He appears as a non-playable character in Call of Duty: Black Ops. In the single-player campaign mission U.S.D.D. he speaks personally with the player Alex Mason inside the Pentagon. 12 days after meeting Mason, John F Kennedy visits Dallas where he is assassinated.
He also appears as a playable character in the Zombies map "Five". His player indicator color is white. While negotiating with Cuba Prime Minister Fidel Castro along with Robert McNamara and Richard Nixon at the Pentagon, zombies invade. The four team up to fight off the zombies.
His username to log in into the CIA data system is jfkennedy with the password LANCER, which is his Secret Service callsign.
Evelyn Cross's letter, dated June 26, 1963, told Kennedy to "reconsider" an unknown final offer from a certain individual. She insisted Kennedy to take the offer "before it's too late."
John Trent's letter, dated November 21, 1963, one day before the Kennedy assassination, was a "last warning" about an unknown event, which likely had something to do with his assassination.
Kennedy appears in a small Easter Egg in Ascension: He can be heard through one of the three red telephones, which start to ring after certain events in Ascension. He says one of his "out-of-ammo" quotes - "Need some beans for the chowder here!"
In Black Ops, Kennedy has two voice actors. In U.S.D.D., he is voiced by Chriss Anglin, who speaks with a realistic depiction of Kennedy's voice. In "Five", he is voiced by Jim Meskimen, who uses an exaggerated New England accent.
In an email from John Trent it states "victory cannot be achieved without sacrifice", something Viktor Reznov says in Vorkuta.