Mafia III is an open-world action-adventure game played from a third-person perspective and the third entry in the Mafia series. Players control Lincoln Clay across a large recreation of the fictional city of New Bordeaux, modeled on New Orleans, tackling missions with a mix of gunplay, melee combat, stealth, and a cover system. Objectives can be approached in different ways, and players seize territory from rival criminal outfits and hand districts to their lieutenants. Period cars can be driven across the city, and the setting and licensed soundtrack draw heavily on the late 1960s American South.

Set in 1968 in the fictional southern city of New Bordeaux, Mafia III follows Lincoln Clay, a young Vietnam War veteran who returns home to the surrogate family that raised him. He agrees to help the local Black Mob settle its troubles, which brings him into the orbit of the powerful Marcano crime family that controls the city. After the mob betrays and murders the people closest to him and leaves him for dead, Lincoln survives and sets out for revenge. With the aid of a former handler and a group of rival power brokers who have their own grudges against the Marcanos, he begins tearing down their operation and building a criminal organization of his own across New Bordeaux.