Mario returns to the stars as the everlasting villain Bowser has kidnapped Princess Peach once more, this time while she was baking a cake. It's up to Mario once again to fight and defeat Bowser and Bowser Jnr, among numerous new villains and obstacles, to save Princess Peach.

The basic goal of each level is to collect the golden star, either by reaching an end goal, collecting a number of smaller star bits, or defeating an end-level boss. The environment is a mixture of standard Mario stages filled with familiar evil characters and miniature planetoids with their own orbital gravity. Certain levels switch the perspective from 3D to 2D, mimicking the platform origins of the character, while others range from molten lava wastelands, ice caverns, or oceans. Unlike Super Mario Galaxy, Galaxy 2 features a more standardized level system, a number of galaxies split into smaller planetary levels that can only be reached by completing one planet, to open up the path to the next. To reach an end-level boss or open a bonus planet, you need to have discovered enough golden stars to unlock it. The hub world of the original has been replaced with a spaceship, shaped like Mario's head, which can be used to travel between Galaxies, as well as discover hidden 1-Ups.

Galaxy 2 features further improvements in gameplay, with two new suits for Mario and the return of his faithful companion Yoshi. Mario's first new suit is the Cloud Suit, which allows him to create three safe but temporary cloud platforms. The second new suite is the Rock Suit which, while wearing it, allows Mario to roll up into a rock ball, which will be necessary to complete some challenges or defeat certain foes. Yoshi adds an element of speed, can eat most enemies in sight, and can reach higher areas that Mario cannot reach alone. The green dino can also eat certain fruit to bolster his move set, but only for a brief moment of time, such as a speed boost, the ability to float higher into the air or to see invisible platforms, especially handy in a Ghost House.

Like the original Super Mario Galaxy a second player can join the experience by pointing the Wii Remote on the screen to collect coins or fling star bits, however, this time they can also collect items that are out of the reach of Mario or Yoshi, and push back enemies in advance of the hero.

To aid those too young or new to the franchise, a second DVD explains the ins and outs of the control system. Plus, if you get stuck along the way, you can also turn on the Super Guide, which gives control of Mario over to the AI to complete a tricky level for you. However, you don't win a proper star as a reward, only a bronze star. Various 'Hint TVs' are also dotted around certain levels to explain or introduce a new element to the gameplay.