Pixel Tactics is a head-to-head game of tactical combat for two players. Each player has an identical deck of 25 cards, from which they draft a leader. The leader's abilities alter vastly the strategy and playability of every other card in the deck, making the game playable in 25 different ways.

In the game, players take turns placing cards and attacking. Each card can activate in various ways, taking on offensive capabilities in the front rows of the unit, or support powers in the back rows. Cards can also be played as orders – powerful single-time effects that can turn the tide of battle.

Play continues until either player's leader is defeated. A typical game is best of three or five rounds.

Mega Man Pixel Tactics: Blue features 28 characters from Mega Man 1-3 — including Mega Man, Dr. Light, and Robot Masters — and these characters are compatible with all other Pixel Tactics games.