Mario Party 6 oferece um novo lote de jogos que exigem seus dedos e sua voz. Nesta parte da série Mario Party, você pode usar o controlador de microfone incluído para abrir caminho para a vitória. Mais de 80 minijogos estão incluídos. Você pode jogar como Mario, Bowser ou outros personagens do Reino dos Cogumelos. Novos personagens aparecem no tabuleiro, dependendo da hora do dia. O jogo suporta até quatro jogadores.

Brighton and Twila – the sun and the moon – watch over Mario Party World from the sky and host the best parties. The two celestial party animals have always been good friends. That is, until the day Brighton asked Twila, "Who's more impressive, you or me?" Brighton and Twila argued furiously over who was more popular and impressive. The sky thundered with the fury of their cataclysmic squabble! Mario and his party-hearty friends tried to get them to make up, but nothing they said could settle their spat in the sky. That's when Mario came up with a brilliant plan to harness the power of the Stars to end the feud! They decided to throw a massive Mario Party to collect Stars and fill the great Star Bank! Determined to end Brighton and Twila's feud, they started partying right away. ...But will the power of the Stars be enough to end the furious feud?