Chao had Spanish parents. His mother, Felisa Ortega, is from Bilbao, Basque country, and his father, writer and journalist Ramón Chao, is from Vilalba, Galicia. They emigrated to Paris to avoid Francisco Franco's dictatorship—Manu's grandfather had been sentenced to death. Shortly after Manu's birth, the Chao family moved to the outskirts of Paris, and Manu spent most of his childhood in Boulogne-Billancourt and Sèvres. As he grew up he was surrounded by many artists and intellectuals, most of whom were acquaintances of his father. Chao cites much of his childhood experience as inspiration for some songs.
Manu Chao sings in Spanish, French, English, Portuguese, Galician, Arabic and Wolof often mixing several languages in the same song. His music has many influences, such as punk, rock, French chanson, Iberoamerican salsa, reggae, ska, and Algerian raï. These influences were obtained from immigrants in France, his Iberian connections, and foremost his travels in Mesoamerica as a nomad following the disbanding of Mano Negra.
Many of Chao's lyrics talk about immigration, love, living in ghettos and drugs and often carry a left-wing message. This reflects Chao's own political leanings—he is very close to the Zapatistas and their public spokesman, Subcomandante Marcos. He has many followers among the European left, the Latin American left and the anti-globalisation and anti-free trade movements. He is also a founding member of ATTAC. Punk and reggae historian Vivien Goldman commented of his work, "I was writing about Good Charlotte and The Police. They adopted the trappings of punk. They aren’t bad groups, but the punk aspect is more manifested by somebody like Manu Chao. He's one of the punkiest artists out there I can think of. It's an inclusionary spirit that is punk."
Though Chao is quite well known in Europe and Latin America, he has not had the same success in the English-speaking world. Tours in the United States with Mano Negra were not as successful as elsewhere and Chao seems inclined to focus his efforts in the places where his musical style finds its roots. Though his live performances in the U.S. are infrequent, Chao played a handful of dates there in 2006, including a headlining show at Lollapalooza 2006 in Chicago, IL. His final appearance on his 2006 U.S. tour was a benefit concert in the Prospect Park Bandshell in Brooklyn, New York on August 7. He returned to that venue in the summer of 2007 for two concerts, part of the multicultural "Celebrate Brooklyn" concert series. The crowd was treated to a nearly two-hour performance, including two encores. Manu Chao also appeared at Merriweather Post Pavilion in Columbia, Maryland to a sellout crowd on June 23, 2007. This was a semi-spontaneous endeavour between Thievery Corporation and Manu Chao facilitated by a new-found friendship developed during Lollapalooza 2006. He was one of the headlining acts at the 2008 Austin City Limits Music Festival and the Outside Lands Music Festival in Golden Gate Park. In January 2012 he was the headline act at the opening night of Sydney Festival, marking his first concert in Australia.
In 2003 he approached Amadou & Mariam and later produced their 2004 album Dimanche à Bamako ("Sunday in Bamako"). His song "Me llaman Calle", written for the 2005 Spanish film Princesas, earned that film a Goya nomination for Best Original Song. It has been released in 2007's La Radiolina. Vocals from the song are included in the Go Lem System song "Calle Go Lem". Time magazine named "Me Llaman Calle" one of The 10 Best Songs of 2007, ranking it at No. 8. Writer Josh Tyrangiel observed,
Chao's warm singing over José Manuel Gamboa and Carlos Herrero's leaping Flamenco counter melody creates a direct emotional line to the core of this mid-tempo ballad. With its easy melody and universal rhythm Me Llaman Calle walks proudly in the shadow of Bob Marley, the last guy who made world music this disarmingly simple.His song "La Vida Tómbola" was featured in the documentary film Maradona by Serbian filmmaker Emir Kusturica. The song "La Trampa", recorded with Tonino Carotone for the compilation album Fuerza! was used as the theme song for the short-lived improvisational comedy Drew Carey's Green Screen Show.
The songs "Bongo Bong" and "Je ne t'aime plus", which appear back-to-back on Clandestino, were covered by British singers Robbie Williams and Lily Allen, who recorded them as a single track, "Bongo Bong and Je Ne T'aime Plus" and released it as a single from the album Rudebox.