Combat in the Bayonetta series resembles that in Hideki Kamiya's prior game, Devil May Cry. The player is encouraged to explore ways to dispatch enemies with as much flair as possible through the use of both melee and long ranged attacks, complex combo strings, and multiple weapons. Special commands or actions are woven into events, finishes, executions, and unique "Torture Attacks" in which Bayonetta summons a variety of devices to deal devastating blows to her enemies. Such devices range from guillotines to iron maidens. Bayonetta also has unique but limited abilities that her enemies do not possess, such as "Witch Time", which activates when the player makes a well-timed dodge to an attack. This temporarily slows time to allow her to inflict massive amounts of counter damage before the enemies can react.
The player can perform many standard action game moves—double jump, lock onto enemies, rotate the third-person view camera, backflip to avoid attacks, swap between weapons on the fly, break apart background objects, and break through doors. Players can unlock the "Beast Within" ability, which allows Bayonetta to transform into a panther or one of various other living creatures to enhance her abilities. Many enemies and objects drop halos when destroyed. The player can collect these halos to buy upgrades and weapons. The player can also use enemy weapons, either to directly attack or as props for movement. Bayonetta's strongest attacks transform her hair into giant heels, fists, or even demon monsters that assault the enemy. Kamiya expects gamers to first complete the game in 10 to 12 hours, but believes that the game's rating system and the pursuit of high scores will provide replay value. The game has a fixed button configuration; Kamiya said, "we found that there wasn't really a point to changing it."
The game includes five difficulty modes: "Very Easy", "Easy", "Normal", "Hard", and "∞ Climax". Only the first three are open to a new player. The player must complete all chapters on Normal difficulty in order to unlock Hard, and all chapters on Hard to unlock ∞ Climax. Unlocking a new difficulty setting with one playable character will also unlock it for all other playable characters.
- Enemy Speed: In general, the easier the setting, the more slowly enemies will move. There will also be longer pauses between attacks.
- Health Regeneration: Health will regenerate over time on Very Easy mode.
- Accessories: On Easy and Very Easy, the accessory "Immortal Marionette" is placed in the inventory and automatically equipped. It can be unequipped by the player.
- Automatic Mode: On Easy and Very Easy, an "Automatic" mode is made available that can be played with only one hand: the game positions Bayonetta to perform attacks on enemies, and the player only needs to press one button at certain points unless they wish to perform their own choice of movements or attacks. Kamiya, who first added such a mode to Devil May Cry, posted a video on the game's official website in which character designer Mari Shimazaki demonstrated the mode (which Kamiya "jokingly called 'Mommy Mode") in Bayonetta.
- ∞ Climax: On ∞ Climax, enemies are positioned very similarly to Hard, however they have more health. More importantly, Witch Time is disabled, (excluding with Selene's Light and Bracelet of Time Accessories, and "Use Witch Time" Alfheims).