Puyo Puyo Tsu is the second game in the series, released in 1994, three years after the prequel. There is more thought into this game than its prequel.

The game introduces the offset feature, which players can reduce the amount of garbage Puyo sent to the playing field or "send back" Garbage Puyo by generating chains. Tsu also introduces "margin time", a mechanic that, after a certain amount of time passes, steadily multiplies the number of Nuisance Puyo that are sent per chain. "All clear," obtained by clearing every single Puyo on the field, gives the player a Nuisance bonus on their next chain.

The game is also notable for being ported on various platforms besides arcade, such as Mega Drive, Sega Saturn, Super Famicom and Sony PlayStation. There are various modes exclusive to certain platforms, and both Sega Saturn and PlayStation versions feature voice-acting.