- Alex Mason is the main protagonist in the 1980s part of the campaign. He first appears at the very beginning of the game’s predecessor, Call of Duty: Black Ops, and later it is revealed that Mason was brainwashed at Vorkuta, but the brainwashing was tampered by Viktor Reznov, which turned Mason against his former brainwashers. Because of these events, Mason suffers from a personality disorder. Depending the circumstances Mason is either accidentally shot dead or wounded and put into a coma for 30 years by Woods during a set up by the main antagonist, Raul Menendez. He is voiced by Sam Worthington.
- David Mason codenamed Section is the main protagonist in the 2025 part of the campaign and the son of Alex Mason and an unidentified woman. David’s relationship with his father was strained, following Alex repeatedly breaking his promise not to return to work for the CIA, specifically following the death of David’s mother. David grows up to become a lieutenant commander in the US Navy Seals and is a part of SEAL Team Six along with his best friend Mike Harper, stationed aboard the USS Obama. At the end of the game, David either kills or captures Menendez and can also reunite with his father if he is spared by Woods. He is voiced by and motion captured by Rich McDonald.
- Mike Harper is a primary character and the “side-kick” of David Mason. He is part of SEAL Team Six along with David Mason. He can either be killed by Farid or he can be spared at the cost of Farid’s life. He also kills Salazar for betraying them if he wasn’t killed by Farid depending on the player’s choice. He is voiced and motion captured by Michael Rooker.
- † “Farid” (Arabic: فريد) is the tech expert from Joint Special Operations Command and is a member of Seal Team Six, where he serves as a mole in Cordis Die. Depending on the players action, Farid is either killed by Menendez if he fails to prove his loyalty by killing Harper, DeFalco when the USS Obama was breached, or Salazar when he took the bullet to save Chloe Lynch. He is voiced by Omid Abtahi. Harper nicknames him “Egghead”.
- † Jason Hudson is a secondary character, who was Mason’s handler and turns out to be the man interrogating him throughoutBlack Ops. Hudson is a good friend of Mason and Frank Woods in Black Ops and Black Ops 2. He is captured by Raul Menendez along with Woods and Mason’s son, David. Hudson sacrifices himself by volunteering to die for Woods and David’s sake. Hudson is voiced by Michael Keaton, replacing Ed Harris.
- Frank Woods is a secondary character, and retired from duty. He is an ally of Alex Mason. He first appears in the first level ofBlack Ops, along with Mason and Bowman, during the Bay of Pigs Invasion. He is presumed dead, but an anonymous note sent to Mason (viewable in the interrogation room computer) states that Woods is still alive and imprisoned in Hanoi. The reveal trailer forCall of Duty: Black Ops II shows he survived and is still alive at 95 but handicapped after a run-in with the game’s antagonist Raul Menendez. Depending on the player’s choices, he either survives the game or is killed by Menendez. He is voiced and motion-captured by James C. Burns.
- Thomas Briggs is a secondary character, who is Mason’s commanding officer and Admiral of the USS Obama. He is either wounded or killed by Menendez during the mission Odysseus. He is voiced and motion captured by actor Tony Todd.
- Chloe Lynch is a civilian and former employee of TACITUS and goes by the name of Karma and the only one that knows how to disable the Celerium Worm. The character is only playable in the “Second Chance” Strike Force mission in Yemen if the player fails to save her from being kidnapped by DeFalco. Depending on the players action, if Farid lives and takes the bullet for her then she will decode the Celerium Worm and restore control of the fleet of drones. If Farid dies then she will be killed by either Salazar or DeFalco, allowing the Celerium Worm to infect the US’s mainframe system and shutting down its system. She is voiced by Erin Cahill.
- Crosby is a soldier who worked with David Mason’s unit in “Celerium” and would later appear in “Fallen Angels” and “Odysseus”. He is wounded when extracting David Mason from the U.S.S. Obama, and is not seen in any later missions, thus his fate is unknown.