Mescudi has released seven studio albums: Man on the Moon: The End of Day (2009), Man on the Moon II: The Legend of Mr. Rager (2010), Indicud (2013), Satellite Flight: The Journey to Mother Moon (2014), Speedin' Bullet to Heaven (2015), Passion, Pain & Demon Slayin' (2016), and Man on the Moon III: The Chosen (2020). He has also collaborated on several mixtapes, including KIDS SEE GHOSTS (2018) with Kanye West, and WZRD (2012) with Dot da Genius.
Mescudi has won two Grammy Awards, for Best Rap Performance by a Duo or Group for "All of the Lights" (with Kanye West, Rihanna, John Legend, and Fergie) and Best Melodic Rap Performance for "Gorgeous" (with Kanye West). He has also received nominations for Album of the Year for My Beautiful Dark Twisted Fantasy (2010) and Indicud (2013), and Best New Artist (2010).
In addition to his music career, Mescudi has also appeared in several films, including Need for Speed (2014) and Bill & Ted Face the Music (2020). He has also created the television series Entergalactic (2022) for Netflix, based on his album of the same name.