Derek and Chris did not come face-to-face in the flashbacks in the early-2000's. Chris seemed to be aware that Derek was a member of the famous and well-known Hale Family just as Derek knew of Chris' Argent heritage. The conflict between the Argent and Hale families had taken a turn for the worse when Chris' younger sister Kate Argent seduced Derek to gain information about the Hale Family and set fire to the Hale House, killing between eight to eleven members of the Hale Family, human and Werewolf alike, though neither Chris nor any other member of the Argent Family had no idea that Kate was the one who orchestrated the fire; instead, it was an event that was always pinned on the whole Argent Family for their reputation as Hunters.
Both Derek and Chris returned to Beacon Hills with the same goal: track down and kill the yet-unidentified Alpha that killed Derek's older sister Laura Hale and stole her Alpha powers. Chris spent the whole season tracking down the Alpha comitting a killing-spree against all of those involved in the Hale House Fire, while also searching for the Alpha's first bitten Beta, not knowing it was actually his daughter Allison's boyfriend Scott McCall. Eventually, Chris learned through Scott's best friend Stiles Stilinski that Kate was the one who killed the majority of the Hale Family and reluctantly teamed up with Derek and Scott, along with Allison, Stiles and Jackson Whittemore, in taking down the Alpha, who was revealed to be Derek's uncle Peter Hale, one of the few survivors of the Hale House Fire, giving Derek the chance to avenge his sister Laura by killing Peter and usurp his position as Alpha of the Hale Pack.
The next season, Chris and Derek returned to enemies when Chris' father Gerard Argent returned to Beacon Hills in order to avenge the death of his daughter Kate at Peter's hands, declaring war against the Beacon Hills Werewolves and swearing to kill them regardless of their innocence or guilt. Derek started building his own pack composed out of some high school students, Isaac Lahey, Erica Reyes and Vernon Boyd, both to stand against the Argents and the imminent arrival of the Alpha Pack. After Gerard forced him to help his wife Victoria commit suicide after she was accidentally bitten by Derek and witnessed his father corrupting his daughter into becoming a ruthless Huntress just like Kate, Chris finally saw Gerard as everything that he despised-- a monster-- and once again teamed up with Derek and Scott to defeat Gerard and turn Jackson from a Kanima into the Werewolf he was meant to be, freeing him from Gerard's control.
In the two halves of Season 3, Chris and Allison decided to return to the Hunter lifestyle, but this time helping the Beacon Hills supernaturals protect their town. Derek and Chris' relationship became stronger as they worked together to lock the moon-starved Boyd and Derek's younger sister Cora Hale and stand against the newly-arrived Alpha Pack, while also investigating the human sacrifices committed by the Darach Jennifer Blake, who was hell-bent on killing Deucalion, her former friend and Alpha Kali and the rest of the Alpha Pack for trying to kill her. Chris became a target of Jennifer's for her guardian trio of sacrifices alongside his friends Melissa McCall and Noah Stilinski, but they were saved through the combined efforts of Allison, Stiles, Isaac, Derek and Scott. Weeks later, demonic demons known as the Oni arrived to search for a dark Kitsune spirit, known as the Nogitsune, forcing Derek and Chris, along with Scott and the other members of his newly-formed pack, to battle against these demons and discovered that the Nogitsune was possessing their friend and ally Stiles. It was during a battle against the Oni that Allison met her end after an Oni stabbed her with its ninjato, traumatizing Chris so much that he travaled to France with Isaac after they managed to avenge Allison by killing the Oni and imprisioning the Nogitsune.
Chris and Derek reunited nearly two months later, after Chris was informed by Scott that his sister Kate had miraculously survived her "death" and was resurrected and turned into a Werejaguar because Peter's claws sliced her throat so deeply that she was turned in the same manner as through a Bite. Derek admitted to Chris that Kate performed a ritual on him that was causing him to lose his powers, not aware that this was actually part of an evolution for Derek to become an Evolved Werewolf like his mother Talia Hale and his sister Laura. Derek and Chris yet-again helped their friends and allies in protecting the numerous supernaturals from Hunters and professional killers willing to kill them for their Deadpool bounties. After the Deadpool was shut down and Kate and her Berserkers were defeated, Derek completed his evolution and became a Werewolf with the rare talent to shift into a real wolf and left Beacon Hills to help his new girlfriend Braeden track down the assassin and Werecoyote The Desert Wolf while Chris parted ways with the McCall Pack as well by joining the Calavera Family in hunting Kate down.
In the penultimate episode of Season 6, Chris traveled to North Carolina, where Derek was investigating the murder of a Brazilian pack of Werewolves at the hands of Gerard, his new protégée Tamora Monroe, and their huge Hunter Army. Chris and Derek returned to Beacon Hills to help the McCall Pack in their war against Gerard and Monroe as well as to defeat the ancient fear-inducing shapeshifter Anuk-ite, who was using its powers to turn the human population against the supernatural creatures living in Beacon Hills. The McCall Pack ultimately emerged victorious in the end of the series, with the Anuk-ite being turned to stone by its own power, Gerard being mauled to death by his own daughter the Werejaguar Kate, and Monroe fleeing from Beacon Hills while recruiting thousands of people all over the world to her cause, forcing Chris and Derek to help the McCall Pack in recruiting fellow supernatural creatures to match Monroe and her army one day.