In The Dark Moon, a flashback to several days prior to the events of the episode showed Scott, Stiles, and Lydia in the animal clinic to discuss Derek's worrisome absence. Scott informed them that after weeks of Derek not returning his calls and texts, he went to Derek's loft to check things out, where he found dozens of bullet casings left all over the floor. He then showed Stiles and Lydia the shells, which had a skull engraved in the brass, and explained that Deaton had told him that it was the symbol of a Hunter family from Mexico known as the Calaveras, who they believed had captured Derek. When Lydia realized that Scott needed her Banshee abilities to figure out Derek's current status, she used the casings to create sounds through which she could divine for more information. Though she heard Derek's screams through the vibrations, she was unable to tell if he was dead or alive, leading Scott to decide that the McCall Pack needed to go to Mexico themselves to try to get Derek back.
Once there, Stiles and Lydia were approached by Severo Calavera at the club inside the Calavera Compound and brought to see the family's matriarch, Araya Calavera, while Scott, Kira, and Malia stayed in the club to try to find Derek themselves. After Stiles and Lydia offered Araya $50,000 from the money they stole from the evidence in the Katashi murder case, and after Scott, Kira, and Malia took out several Calavera Hunters, the three went into a back hall to look for Derek, where they were overwhelmed by wolfsbane fog and incapacitated. When Araya confronted Scott, he insisted that all they wanted was Derek, and Araya assured him that she knew. However, even through the haze of wolfsbane, Scott correctly guessed by Araya's expression that she had no idea where Derek was either, causing her to shock him in the chest with a taser wand.
The next morning, Araya and Severo then began to torture Scott under the guise of testing him, informing Scott that she was trying to find Derek as well and insisted that he knew who took him, giving him hints that it was a shapeshifter who was turned, but not by a bite, and that it was someone with a particular vendetta against the Hale Family. Scott finally realized that Derek had been captured by Kate Argent, who had survived her clawed-out throat at Peter Hale's hands and had become a werejaguar.
Satisfied, Araya sent the McCall Pack off with Braeden, a mercenary she had hired, believing that together they would all get what they wanted-- Kate captured (for the Calaveras), and Derek returned home safe (for the pack). Braeden led the group to La Iglesia, a church built over the ruins of the Temple of Tezcatlipoca, where she believed Kate was holding Derek. After the Jeep broke down, Braeden and Scott ultimately were forced to go on without the others, who planned to catch up with them once the Jeep was repaired. Once there, Scott and Braeden ran into Kate's Berserkers, who were eventually scared away by Scott's Alpha roar, allowing them to finally locate Derek behind a wall with Tezcatlipoca's seal over it. However, once Scott punched through the wall, he found that Kate had de-aged Derek back to his sixteen-year-old self for reasons unknown, stunning him, Braeden, and the rest of the pack.
In 117, upon returning to Beacon Hills, Scott, Stiles, and Lydia brought the de-aged Derek to the animal clinic, hoping that Deaton would know what to do. However, Deaton insisted this was beyond his expertise and assumed that Kate did it for a reason, which would probably not be good for any of them. With Derek asleep and having no answers to how to help him, Scott and Stiles left him with Lydia and Deaton and returned home. The next morning, Derek woke up while Deaton and Lydia were testing his powers, and he was so overwhelmed with fear, since he didn't recognize them, that he fled the clinic, forcing them to call Scott and Stiles back for assistance. They debated what to do about the fact that this version of Derek had no idea about the Hale House Fire that killed his family, with Scott ultimately deciding to be honest with Derek, since, as a werewolf, he would know if he was being lied to about it.
Scott and Stiles eventually caught up with Derek after he was arrested for assaulting an officer when Deputy Haigh caught him at the Hale House ruins, where Scott showed him his red werewolf eyes to assure Derek that he could trust him. However, when Derek asked about his family, Scott didn't have the heart to tell him the truth about what happened, instead claiming that Derek had lost a great deal of memories and that his house burned down but his family was fine and had moved away for their own safety. Scott felt incredibly guilty for lying to Derek about this, but Stiles assured him that it was in Derek's best interest, believing that once they turned Derek back to his adult self, it wouldn't matter. Unfortunately for them, Derek figured out that they had lied when he asked Rafael McCall about the fire, and afterward, Derek refused to talk to Stiles, insisting that he would only talk to Scott since he was the Alpha and trusted his judgment.
Because of this distrust of Stiles and being in his teenage mindset, Derek was easily manipulated by Kate Argent into opening the Hale Vault, which seemed to have been the reason for de-aging him in the first place. However, when he heard Scott roaring outside of the vault while he fought the Berserkers with Malia, he somehow knew that it was Scott and that he was in trouble despite still not knowing him well. Ignoring Kate's protests, Derek ran away to help Scott fight, which somehow allowed him to age back to his adult self. When Derek's eyes flashed gold instead of blue, Scott stared at Derek in shock.
In I.E.D., Derek appeared in the Beacon Hills High School boy's locker room and taunted Liam Dunbar by pretending to break his lacrosse stick in order to gauge how strong he was and how much control over his werewolf transformation. After getting Scott's newly-bitten Beta in a choke-hold, he remarked, "You're right, Scott-- he is strong," revealing to Liam that Scott was supervising the entire confrontation. After Scott sent Liam off to class, Derek smiled and informed Scott that he was going to be good at being an Alpha to Liam, but Scott, visibly overwhelmed, exclaimed that he was totally unprepared, and that he would need to upgrade Derek's earlier offer of mentorship to a "full-on training manual."
Scott then sat down on the nearby bench with Derek and confessed that he thought this semester was going to be when he was able to focus on school and his human life again before reminding him of all of the newest complications in their supernatural lives, including the newly-turned Beta Liam, the revelation that Kate was a werejaguar and back in Beacon Hills, and the fact that there was a Deadpool hit-list with all their names on it. Derek assured him that they would get through it and stated that the Deadpool should probably be their first priority before asking him if the pack had made any headway on breaking the second part of the list. Scott informed him that Lydia, Kira, and Malia had spent the entire weekend at the Martin Lake House to try to figure it out in the Banshee study, but with little success.
In Weaponized, Derek was at the hospital where Braeden was being treated for a gunshot wound to the abdomen when he learned from Melissa McCall that Scott, Stiles, Malia and Kira had been exposed to the same virus that Braeden saw kill numerous members of Satomi Ito's werewolf pack. Teaming up with Melissa, Alan Deaton, and Satomi, Derek assisted the group in figuring out what the pack was dealing with so that he could save Scott and the rest of the pack from the virus. During a conversation with Satomi about her friendship with Derek's mother Talia, where Derek remarked that he hated the tea they drank that smelled awful, Deaton realized that the tea, made of wild purple reishi mushrooms, had inoculated Satomi and prevented her from getting sick, which meant it could also be used as a cure. Derek remembered that his family had a jar of the mushrooms in the Hale Vault and instructed Melissa on how to find them so she could get a message to Scott.
In Perishable, after witnessing Jordan Parrish surviving being burned alive, Lydia immediately brought Parrish to Derek's loft so that Derek and Scott could try to figure out what he was. Derek was shocked to learn that Parrish had been doused in gasoline before being set on fire (especially after Lydia pointed out that his hair and nails were still perfectly fine, and should be gone after what happened), but he had little idea of what Parrish could be. Scott reminded him that he knew that Jackson Whittemore was a Kanima and that Kira Yukimura was a Kitsune, but Derek insisted that this was beyond his level of experience. Parrish, overwhelmed and not understanding what any of them were talking about, demanded to know if they were "psychic" like Lydia, which got a chuckle out of both Scott and Derek. However, after remembering that Parrish was on the Deadpool just like them, Derek eventually encouraged Scott to reveal himself as a werewolf to Parrish.
Scott and Derek, along with Parrish, then listened to Lydia explain what she had learned about her grandmother Lorraine Martin, who was also a Banshee, and who she believed had written the code used to encrypt the Deadpool lists. Afterward, Scott was looking around the loft when he saw a handgun laying on Derek's bed and picked it up. Derek teased him about being careful with it and took the gun back, though his demeanor became more quiet and uncomfortable when Scott brought up the fact that Derek doesn't like guns. When Scott correctly guessed that this had something to do with Derek's werewolf eyes changing from blue to gold, Derek sighed and admitted that whatever Kate Argent had done to him was still affecting him, causing him to lose his powers, to the point where he now couldn't transform at all. This worried Scott so much that he felt compelled to admit that Derek's name had unlocked the last portion of the Deadpool list, which, as Derek pointed out, put him among the other key words of "Aiden" and "Allison", both of whom were dead. Scott brought up the fact that since they were all names predicted by a Banshee, it could mean that Derek was in danger, but Derek sadly reminded him that Banshees don't predict danger-- they predict death.
The next evening, after Braeden had interrogated Deputy Haigh and learned that his cronies were planning on killing Scott, Malia, and Liam, she quickly passed the information on to Derek. Meanwhile, Scott, Malia, and Liam had been weakened with subsonic frequencies and had been doused in gasoline just like Parrish had earlier, but before the lead security guard could light them on fire, Mason Hewitt managed to shut off the frequency so Scott could steal the lighter back from the guard. Before they could react any further, Derek and Braeden arrived, using hand-to-hand combat to fight and disable the guards before they could kill Scott and the others. Scott flinched when Braeden was forced to snap the leader's neck after he tried to grab his gun, but was otherwise relieved by their quick rescue. When Derek held out his hand to help Scott to his feet, Scott asked him what happened to his gun, and Derek snarkily reminded him that he was covered in gasoline, making the use of guns unsafe. Scott just replied with, "Oh, yeah..." as Derek patted him on the back and moved to help out Liam and Malia.
In Monstrous, Scott was summoned to the animal clinic by Kira, who revealed that she had found Satomi and the rest of her pack, including Brett Talbot and Lorilee Rohr. Upon seeing that roughly eight members of the pack had survived the modified canine distemper virus, Scott determined that they were going to need a lot more help to protect them from the dozens of professional Hunters who had descended upon Beacon Hills to take out the rest of the people on the Deadpool.
To protect Satomi's pack, Scott brought them all to Argent Arms International to hide out before summoning Chris Argent, Derek, and Braeden for backup. Derek reacquainted himself with Satomi's pack, but pointed out to Scott that though they may have fangs and claws, they weren't fighters like their pack. When Scott replied that he called Derek for that reason, Derek reminded him that he no longer had fangs and claws, either, leading Braeden to interject that he had called her for that reason. After a brief debate between Kira, Scott, Braeden, and Brett, Derek gave the group a motivational pep talk to help them get through the impending attack, arguing that regardless of whether the people coming after them were professional assassins, hunters, or amateurs with guns like himself, they should make it clear to anyone trying to kill them that doing so would result in them being put on their own Deadpool.
Scott and Derek then fought along with the rest of the McCall Pack and their allies, including Satomi and Brett, while the others in Satomi's pack hid for their own safety. Scott and Derek only sustained minor injuries during the fight, though Derek's lack of a regenerative healing factor made his slightly more concerning, and once Stiles and Malia managed to shut down the computers that automatically ran the Deadpool, the fight ended, and the hunters who invaded the warehouse immediately fled to avoid retribution.
In A Promise to the Dead, Scott, feeling guilty about having held onto the duffle bag full of cash he had taken from Garrett, which was from the $117 million that was stolen from the Hale Vault, decided to finally return the money to Derek after a serious conversation with his mother, Melissa McCall. However, Derek accepted Scott's reasoning for taking so long without question, kindly pointing out that he understood Scott's family's money issues and reminding him that even True Alphas could be tempted. Derek went on to say that he had his own money, and that all of the bearer bonds in the vault belonged to Peter, before echoing Stiles' earlier sentiments that they would all likely be better off if the rest of the stolen money never resurfaced.
Scott then changed the subject to the events of the previous night, as he knew that Lydia Martin had unconsciously been drawn to Derek's loft in a Banshee fugue state before wailing for his death. He assured Derek that Alan Deaton was looking into it, and that if anyone could figure out what was happening to Derek and stop it, it was the extremely knowledgeable Druid. That night, Derek allowed Scott to use his loft to have a much-needed date with his girlfriend, Kira, and likely helped him set up dozens of lights to create a romantic atmosphere. However, when Braeden and Derek returned later that night to find the large wall of windows shattered, the loft wrecked, and Scott and Kira nowhere to be found, Derek wasted no time calling Stiles and Sheriff Stilinski to inform them that he believed Kate Argent and the Berserkers had taken him.
In Smoke and Mirrors, Derek and Braeden were taking inventory of all of their weaponry and ammunition as they prepared to leave for Mexico to rescue Scott and Kira. Upon realizing that Derek didn't believe he would survive the rescue, Braeden insisted that she was not okay with Derek dying, leading him to confess that he was perfectly content with the possibility if it meant saving Scott and Kira.
Since Scott wasn't there, and the full moon was that night, Derek volunteered to help Stiles restrain Scott's new Beta Liam in the back of a prison transport van that Braeden had obtained while on their way to La Iglesia. Though Liam did ultimately break free and nearly kill Derek and Stiles, they were able to help him regain control by using Satomi's Pack's Buddhist mantra, and Derek was so impressed by Liam's ability to rein himself in that he asked if Liam could use his newfound control to help them rescue Scott and Kira, to which Liam assured him that he could. However, as soon as they departed the vehicle, Derek was gravely injured after one of Kate Argent's Berserkers stabbed him several times in the chest, and rather than allowing the others to help him, he insisted that Stiles take Peter, Malia, and Liam with him to save Scott, leaving only Braeden behind to comfort him.
Fortunately, though it seemed as though Derek had died, he had actually evolved into a Beta who could full-shift into a true wolf like his mother, his sister, and his cousin. Meanwhile, Scott, who had been turned into a Berserker by Kate, had been broken free of this new transformation with Liam's help, allowing the McCall Pack to work together to defeat Kate and Peter and kill the rest of the Berserkers. Afterward, Derek nodded in acknowledgement of their good work before he left with Braeden, though it seems that he and Scott had an official goodbye before he left Beacon Hills for good.