Head-to-Head Mode is an additional multiplayer mode featured in Punch-Out!! (Wii). In this mode, two players can battle each other one-on-one via a split-screen view. Giga Mac is accessible in this mode as a power-up after gaining energy from successfully striking the opponent a number of times.
- To date, this is the only multiplayer mode in any Punch-Out!! title.
- The second player plays as a version of Little Mac with a red and yellow outfit and blonde hair. This character bears a slight resemblance to the version of Little Mac from Super Punch-Out!!.
- The special headgear from the main campaign which blocks all damage to the player's head is inaccessible in this mode.