An ichorous green meteor plummets through the Earth's atmosphere, fracturing and showering the earth with glowing green space dust that affects all forms of life nearby. Some plant life - mushrooms and cacti - acquire sentience while, the meteor twists and mutates other life forms, transforming insects and animals into semi-intelligent, warlike communities.

The story of Mushroom Men is told in Acts, each Act occurring in a completely unique environment. Each version of the game (DS and Wii) tells different portions of the history of the Mushroom Men universe. The DS and Wii versions are completely different stories from