Fallout 4 is an open world role-playing game in the style of its predecessors, Fallout 3 and Fallout: New Vegas. Returning gameplay features include the ability to switch between first-person and third-person perspectives, an open world with free roam exploration, a variety of combat options (including guns, explosives, unarmed, and melee), numerous sidequests along with a more linear main questline that branches toward its conclusion, dialogue options that influence the route of a conversation, and the selection of companions that aid in battle.

The S.P.E.C.I.A.L. skill system also makes a return, allowing the player to decide the importance of certain skills to their character (S.P.E.C.I.A.L. being an acronym for Strength, Perception, Endurance, Charisma, Intelligence, Agility, and Luck) upon leveling up. The function of perks is altered, as they are now attached to a skill tree with availability dependent on the rank of the S.P.E.C.I.A.L. skills that they're associated with. The Intense Training perk is replaced by the optional ability to improve the rank of any one of the S.P.E.C.I.A.L. skills by leveling up, in the place of selecting a perk. The Pip-Boy can be acquired early on, and provides access to the player's statistics, inventory, maps, and quest information as in previous games, with the added function of playing mini-games that can be found throughout the Commonwealth. The player can also make use of the Pip-Boy app in order to access the Pip-Boy menu, rather than using the in-game function. HP (health points) and AP (action points) make a return as primary statistics, with the removal of weapon and armor condition. Stimpaks, beds, and other types of consumables such as water or TV dinners can be used to restore HP. Unlike in previous games, exposure to radiation directly influences the player's max health, and can only be reduced through RadAway or paid assistance from a doctor. AP restores over time, and can be used to sprint or attack using the Vault-Tec Assisted Targeting System (V.A.T.S.), slowing down time and giving the player the ability to select a target with success in combat dependent on accuracy, which itself is dependent on factors such as weapon range, distance of the target, and obstruction of the target.