Call of Duty: Infinite Warfare is the thirteenth primary installment in the annual first-person shooter series. It continues the futuristic direction of the previous games, now introducing combat in outer space along with fights in zero-gravity environments. As usual it combines a single-player campaign, a zombies game mode and a full multiplayer mode.

The single-player campaign is set in a distant future where most of Earth's natural resources have been depleted. Through the population and industrial expansion, United Nations Space Alliance (UNSA) is established as a political organization to handle and negotiate all aspects of human space colonization. Different organizations attempt to control the colonies, most notably Solar Associated Treaty Organization (SATO) which is opposed by the hostile faction Settlement Defense Front (SDF). The game focuses on the moment when SDF attacks UNSA, severely weakening its defenses on Earth. The protagonist is Tier 1 Special Operations pilot Captain Reyes, part of the military outfit Special Combat Air Recon (SCAR) tasked with defending UNSA. Only two major warships survive the attack and Reyes is on one of them called Retribution. As one of the few surviving officers he soon receives command of the vessel which then acts as a central hub.

The different missions often stress a guerrilla approach with stealth elements against the much stronger SDF. In space this is done through sneaky light speed jumps. Most of the SDF opposition consists of drone soldiers. There are also aerial combat dogfight missions in space with free movement using a smaller fighter ship called Jackal. From the main ship's bridge both primary and optional missions can be started, with the latter called Ship Assaults unlocking new perks, weapons and gear. A notable side character is Ethan, a fighter drone with a personality. Reyes can use a grappling hook to navigate zero-gravity environments combined with boosts. He also has a wrist computer to control machines and hack enemy gadgets. The campaign introduces two new difficulty modes: Specialist and #YOLO. In the first Reyes' movement can be affected when he is shot in the legs, he can shoot weapons out of the hands of opponents and health regeneration is only possible through nano shots. The other one, #YOLO, introduces permadeath instead of restarting at checkpoints.