He has directed well-known videos for artists such as Queens of the Stone Age, Christina Aguilera, Beyoncé, Blink-182, Blondie, Duran Duran, Lady Gaga, David Guetta, Jamiroquai, Lenny Kravitz, Madonna, Paul McCartney, Metallica, Moby, Ozzy Osbourne, P!nk, the Prodigy, the Smashing Pumpkins, Rammstein, Britney Spears, the Rolling Stones, U2, Robbie Williams and Ghost.

In 1997, he directed the video for the Prodigy's "Smack My Bitch Up", which sparked controversy due to its depiction of drug use, violence, and nudity.

He directed the music video for the Smashing Pumpkins' song "Try, Try, Try", from which a short film entitled Try was spawned.

He also directed the documentary film I'm Going to Tell You a Secret about Madonna and her concert special The Confessions Tour: Live from London.

Åkerlund's other work includes the controversial music video for Rammstein's "Pussy", the video for the song "Telephone" by Lady Gaga and Beyoncé, "Moves like Jagger" by Maroon 5 and Christina Aguilera, and Duran Duran's single "Girl Panic!