It Takes Two is a cooperative action-adventure game designed exclusively for two players, playable in local split-screen or online. Players control Cody and May, a married couple transformed into dolls, as they travel through fantastical environments based on their home and relationship. Gameplay combines platforming, puzzle-solving, and action sequences, with each level introducing new mechanics and giving the two characters different abilities that must be used together to progress. The game frequently changes its core mechanics from chapter to chapter, incorporating sections involving shooting, racing, flight, and other genres.

Cody and May, a married couple planning to divorce, break the news to their daughter Rose. Upset, Rose takes handmade dolls resembling her parents into the family shed, and her tears cause Cody and May to become trapped inside the dolls. They are confronted by Dr. Hakim, an anthropomorphic relationship therapy book who says he has been tasked with fixing their marriage. As Cody and May try to find a way back to their human bodies, Hakim places obstacles and collaborative challenges in their path, forcing them to work together. Along the way, they encounter personified versions of their neglected possessions, rediscover their individual passions, and are reminded of what brought them together.