The gameplay features the return of Dante and Nero as playable characters, along with a new character, named V. The gameplay is similar to that of the other titles in the Devil May Cry series, focusing on fast-paced "stylish action"; the player fights off hordes of demons with a variety of attacks and weapons. They receive a style rating for combat based on several factors, such as move variety, the length of a combo, and dodging attacks. The game's music changes based on the player's performance in combat. Every time the player interacts with the mechanic Nico or finds a statue, they can buy new abilities for each character. While there are three playable characters, the game forces the player to use only one per mission. Like previous games, this title has a Bloody Palace mode where players can face multiple types of demons in a single area.
The first character is Nero, introduced in Devil May Cry 4. He retains his Red Queen sword for melee combat and the Blue Rose double-barreled revolver. However, he does not have his Devil Bringer from the beginning. Instead, he now has an assortment of new robotic arms called Devil Breakers. These have various functions, such as grabbing enemies from a distance or stopping time to freeze an enemy in place. Nero can also find Devil Breakers during stages. Devil Breakers are powerful but fragile and can be destroyed if misused. Late in the story, Nero regains his Devil Bringer and has access to a super-powered state known as the Devil Trigger, which allows him to transform into a demonic form and expand his combat skills.
Dante plays like his Devil May Cry 4 portrayal as he can change between four styles to create new techniques or parry enemy attacks. Along with his signature blade "Rebellion" and the Demonic "Devil Sword Sparda", Dante uses three new Devil Arms, a pair of buzzsaw-like weapons that combine into a motorcycle called "Cavaliere", and a set of fiery gauntlets and boots called "Balrog". Dante also wields "King Cerberus", a stronger version of the "Cerberus" nunchaku introduced in Devil May Cry 3. He also wears the "Dr. Faust", a hat that expends Red orbs to attack; forcing the player to consider risk versus rewards in combat. Dante can also use both the "Kalina Ann" rocket launcher from Devil May Cry 3 and the new enhanced "Kalina Ann 2," or both at once. Besides the Devil Trigger that enhances Dante's abilities and gradually restores his health, the character also possesses a more powerful form named "Sin Devil Trigger" which enables new means of attack.
The third playable character is V, who primarily summons his three demon familiars to fight. These include Griffon, an eagle that uses ranged lightning-based attacks; Shadow, a panther that forms blades, spikes, and portals out of its body; and Nightmare, a large and powerful golem. V enters a Devil Trigger-like state, which turns his hair white, to summon Nightmare, which uses a combination of melee attacks and explosive laser beams. V's familiars are incapable of killing enemies; once their health bar turns light purple, V can use his cane to destroy them with a final blow.
Vergil reappears as a playable character in the game's Special Edition, carrying over his playstyle from the fourth game's Special Edition, including the Concentration gauge mechanic and weaponry. However, the Force Edge from previous Special Edition games is replaced with Mirage Edge, an ethereal sword that Vergil usually uses as a projectile summon. He has a new ability, which allows him to turn into V and gather his trio of demonic familiars to perform a variety of devastating attacks. Instead of transforming into his regular Devil Trigger form, Vergil immediately transforms into his Sin Devil Trigger form. His original Devil Trigger is now replaced with Doppelganger, a summoned spectral copy of his Sin Devil Trigger form which mirrors Vergil's attacks while using the Yamato; which was a mechanic introduced in Devil May Cry 3 as Dante's Doppelganger Style, then reintroduced as the Devil Trigger ability for Vergil in DmC: Devil May Cry reboot.