Yakuza 6 is an action-adventure game set in an open world environment and played from a third-person perspective. It is similar to that of other Yakuza titles with exploration mixed with arcade style beat 'em up combat with ragdoll physics. Yakuza 6 was the first game in the series to use the new Dragon Engine game engine (later used in Yakuza Kiwami 2, Yakuza: Like a Dragon and the spin-off Judgment series), which overhauls the presentation and combat mechanics compared to past games. It also features an advanced variant of Yakuza 5's Dragon Spirit Mode, called Extreme Heat Mode, where Kiryu becomes resistant to knockback as long as his Heat remains, and his combo finishers can turn into Heat actions that take out immense amounts of health. Additionally, as is also later used in Yakuza Kiwami 2, the game categorizes experience points into different types and the player can grant themselves various upgrades by using experience of the correct type; experience points can also be earned by eating at restaurants, though doing this raises the hunger gauge which limits how much food the player can eat and reduces itself with time.
Unlike Yakuza 4, Yakuza 5 and Yakuza 0, Yakuza 6 does not feature any playable characters besides Kiryu himself. Additionally, unlike 0 and Yakuza Kiwami, Kiryu only uses one fighting style. This game features the series staple location of Kamurochō, Tokyo, as well as a new city, Onomichi, Hiroshima Prefecture. Onomichi stands out from other cities in the series in that its name is the same as its real world counterpart, with the area featured in game being a recreation of the city's Shingai district.