After Fela's death in 1997, he became leader of the band, fulfilling his father's wishes. During his teenage years, he divided his time between the band and school, and became interested in football; at 18, he began to devote himself to music full-time. Initially, his shows are a mix of his father's songs (also unreleased) and his own. Over time, he began to add his own touch to the music, delving deep into various African traditions to reflect the struggles and cultures of the continent. His debut record, Seun Kuti & Fela's Egypt 80, was first released by WM Recordings in 2008. Although many outside Africa criticised him for using the name Egypt 80, critics appreciated his musical drive and improvisational fervour. In the same year, Mr Bongo also released his set Many Things. In recent years, Seun has toured the world, playing in front of enthusiastic audiences in Detroit, New York, Los Angeles, Chicago, Philadelphia, Paris, London, Tokyo and especially Lagos. In 2011 he released From Africa with Fury: Rise on Knitting Factory Records. The record was co-produced with Brian Eno and John Reynolds. It proved to be his breakthrough, entering the international Billboard and digital charts.

Seun Kuti & Egypt 80 have continued to tour the world non-stop, often playing multi-hour shows, based as much on group improvisation as on composition. The music never deviated from the overtly political aspect. Over the years, Seun Kuti has continued to affirm that 'Fela will always be number one', despite the fact that he was changing and transforming Afrobeat with his own ever-evolving musical signature. "As the son of Afrobeat icon Fela Kuti, Seun Kuti carries a torch for infectious grooves and political songwriting." - NPR

On 9 December 2022, he released his new EP entitled African Dreams. The EP, featuring Roots frontman and MC extraordinaire Black Thought. It consists of three remixes of tracks from Black Times, Seun Kuti & Egypt 80's 2018 Grammy-nominated album. The ep made it to the top20 on the US independent radio (NACC) chart, top3 on the hip hop chart, and top5 on the world chart. In 2023, Janelle Monae released her new single 'Float' featuring a collaboration with Seun Kuti & the Egypt80.