Dead Presidents opens in 1968, as Anthony (Larenz Tate) is about to graduate from high school. Not wanting to go to college, but needing to get away from home to find himself, he enlists in the U.S. Marine Corps shortly after graduating high school. He is sent to Vietnam, leaving behind a middle-class family, a pregnant girlfriend (Rose Jackson), and a small time crook, Kirby (Keith David), who is like a second father.
Drafted into the military are two of his close friends, Skip (Chris Tucker) and Jose (Freddy Rodriguez). He also meets the gung ho lieutenant, Dugan (Jaimz Woolvett) and his wartime friend, Cleon (Bokeem Woodbine), a religious yet deadly staff sergeant. During their tour in Vietnam as members of a Force Recon unit, they experience the horror of war, losing several fellow Marines during combat. The Marines (specifically, Cleon) also commit atrocities, including executing enemy prisoners and beheading corpses for war trophies. One of their squad is the victim of terror tactics of the North Vietnamese; D'ambrosio (Michael Imperioli) is disemboweled and castrated alive. While waiting for medevac, Anthony, succumbing to the request of the dying D'ambrosio, gives the man a fatal dose of morphine. One of their squad is killed by stepping on a land mine and a night ambush ensues with NVA troops and half of Anthony's team is killed; Dugan is killed after Skip "freezes up" during the gunfight when he is ordered to cover him. Cleon manages to hold off the enemy long enough for Anthony and the last of the crew to escape.
When Anthony finally comes back to the Bronx in 1973, after two tours of duty and attaining the rank of sergeant, he discovers that returning to "normal" life isn't easy or pleasant. He finds his friend Skip, who used drugs during the war, is now a heroin addict. Jose after serving as a demolitions expert, during which he lost his hand, has become a pyromaniac. Cleon is now a devoted minister. And Kirby has since become legitimate due to police cracking down on his criminal business. Anthony is laid off from his job in a butcher shop and finds himself unable to support his daughter. His girlfriend admits to sleeping with another man to provide for her daughter (who may not even be Anthony's). Anthony meets his girlfriend's sister Delilah (a member of the "Nat Turner Cadre", a fictional group similar to black revolutionaries) who always loved Anthony and decides to help him with an idea to get some money. Anthony, Kirby, Skip, Jose, Delilah and Cleon plot to rob an armored car making a stop at the Federal Reserve Bank of Brooklyn.
Skip and Cleon act as lookouts, Kirby is the getaway driver, Delilah waits in a dumpster across the street and Anthony and Jose hide under the loading docks, all armed. Though they plan the heist very carefully, it goes horribly wrong when a policeman stumbles on the scene. The policeman interferes resulting in Kirby attacking him only to be shot in the arm and Skip shooting him in the head. The security guards engage the robbers in a gunfight, ending with Anthony and Delilah killing most and Delilah dying while saving Anthony as the truck leaves. After Kirby tries to block the truck with his car, Jose makes use of an excessive amount of explosives, destroying the armored car and burning most of the cash. They escape with what money is left, but Jose is killed after being struck by a police car.
The surviving four try to lay low after the robbery. Cleon doesn't do so as he begins handing out cash to the churchgoers and buying a new Cadillac car which he obviously can't afford. Anthony and Skip give out presents to poor children on Christmas. Cleon is finally arrested at his church and gives up the other thieves. NYPD storm Skip's apartment to find that he has died of a heroin overdose. As Kirby and Anthony prepare to leave the country, they are attacked at Kirby's pool hall by the police and arrested (though Kirby may have been killed while trying to let Anthony esc