Mass Effect 3's combat is similar to that of Mass Effect 2, but significantly different to that of the original Mass Effect.

Both biotic and tech abilities are effective for dealing damage in combat, and cooldowns are global, but depend on the ability used. For example, Throw may cause a 2 second cooldown (on all abilities), whereas Warp causes a 4 second cooldown (again, on all abilities). Cooldowns are affected by the weight of the weapons you are carrying (you can carry anything from two to five weapons).

Any class can use any weapon, but the weight mechanic means that power-heavy classes need to use lighter weaponry. Each weapon can be assigned up to two mods, which improve the weapon's effectiveness. The same mods can be used on multiple weapons, but mods are specific to a category of weapons (for example, shotguns).

Biotic and tech abilities can combine to form deadly explosions. For example, using Singularity on an enemy and then Warp will detonate the Singularity.

Teammates can be ordered to use certain abilities as before; opening the ability screen slows down the game and allows Shepard to use abilities himself or order his teammates to use them. Each teammate has their own cooldown.

One final change is that Shepard possesses a new and improved melee: holding down the melee button unleashes a powerful melee attack that can kill weaker enemies and stagger stronger ones. However, this attack is slow and leaves Shepard open to enemy attacks.