"American Assassin" follows the rise of Mitch Rapp (Dylan O'Brien), a CIA black ops recruit under the instruction of Cold War veteran Stan Hurley (Michael Keaton). The pair is then enlisted by CIA Deputy Director Irene Kennedy (Sanaa Lathan) to investigate a wave of apparently random attacks on both military and civilian targets.

Together the three discover a pattern in the violence leading them to a joint mission with a lethal Turkish agent (Shiva Negar) to stop a mysterious operative (Taylor Kitsch) intent on starting a World War in the Middle East.