He was born in the late 1950s to Senegalese parents in Bobo Dioulasso in Burkina Faso and began playing drums and singing at an early age.
He joined Orchestre Volta Jazz, a Bobo variety band that played Cuban and Congolese pop songs as well as traditional Burkinabé music. Lô moved to Senegal in 1978, performing in several mbalax outfits. By then, the Zairean sound was in full flower, Camerounian makossa was coming on strong, and reggae had entered the mix, and Lô absorbed everything. In 1985, he was playing guitar with numerous Côte d'Ivoire and French musicians, which led him to record material in Paris in 1987. After his band dissolved, Lô remained in Paris as a session musician, developing his own sound, described as a mix of mbalax, reggae and soukous influences. He spent most of his time in recording studios, and he picked up as much as he could. His casual contacts with Zaire's most successful progressive singer, Papa Wemba, were especially memorable. "I was a drummer. So when there was a group who came and didn't have a drummer, I would practice with them. Papa Wemba's drummer was also a businessman, so if he wasn't there, I would help out. He's from the school of Tabu Ley, and when I was young, I listened to Tabu Ley a lot."
In 1995, Youssou N'Dour offered to produce Lô's debut album, Ne La Thiass, which became a success worldwide.
In 2000, Lô sang alongside Ibrahim Ferrer on "Choco's Guajira", from Cuban pianist Rubén González's, (Buena Vista Social Club) album Chanchullo.
In 2002, he appeared on two tracks of the Red Hot Organization's tribute album to Fela Kuti, Red Hot and Riot. He collaborated with Les Nubians and Manu Dibango on one of the tracks, "Shakara / Lady (Part Two)."