Juanes was born in Medellín, Colombia. He is the oldest child of Alicia Vásquez and Javier Aristizábal. His father called him "Juanes", a contraction of his "Juan Esteban", which he later used as an alias. At age seven, Juanes learned to play the acoustic guitar from his father and older brothers, playing traditional Latin styles such as bolero, tango, cumbia, vallenato, and guasca. During Juanes' childhood, he lost several people close to him; his cousin was held for ransom and executed when the ransom was paid, a close friend was killed by gunmen, and his father died of cancer. When Juanes became a teenager, his music gained a darker sound influenced by heavy metal music, especially that of American band Metallica.

Juanes started the metal band Ekhymosis in 1988, and it released its self-produced, self-titled debut album the same year. The band released five studio albums during its career and shared the stage with acts including Alejandro Sanz, Aterciopelados, and Ricky Martin; however in Juanes' words, the band "couldn't get out of Colombia" and remained "very local and confined to the Colombian market." Juanes disbanded the group in 1998 so that he could pursue a solo career.

In 2000, Juanes released his solo debut Fíjate Bien (Take a Good Look), produced by Gustavo Santaolalla. The album fared well in Colombia, spending ten weeks at the number one position. The album earned him three Latin Grammys for Best New Artist, Best Rock Solo Vocal Album, and Best Rock Song, and Juanes performed at the award show. Later that night, Juanes brought demos for over forty new songs to Santaolalla's studio, ready to begin work on another album.

His second album, Un Día Normal was certified platinum throughout much of the Spanish-speaking world, and its lead single "A Dios le Pido" topped singles charts in twelve countries. Mi Sangre, his third album, fared equally well with Juanes promoting it on a tour with over 200 performances. The album's third single, "La Camisa Negra", generated controversy after being used as a symbol for Italian neo-fascism. Juanes is one of the best-selling Colombian musicians, having sold more than ten million albums and won twelve Latin Grammys. Juanes is also known for his humanitarian work, especially with aid for Colombian victims of anti-personnel mines.

On March 16, 2008 Juanes organized a concert as a response to the 2008 Andean diplomatic crisis. This concert took place on the Colombia-Venezuela border. This was a free event and gathered an audience of 300.000 people. It was broadcasted by Colombian and Venezuelan television stations. A Yahoo-Telemundo partnership webcasted the event. The concert featured the well-known artists: Miguel Bose, Alejandro Sanz from Spain. Juan Luis Guerra from the Dominican Republic, Ricardo Montaner from Venezuela, Juan Fernando Velasco from Ecuador and Juanes and Carlos Vives from Colombia. The concert became a reality with the help of many private companies from Colombia and Venezuela. As an important remark concerning this event, Colombian president Alvaro Uribe had expressed days before the concert that he would attend the event. Juanes' manager replied that since it was an artistic event with no political affiliations they preferred the president not to be present. President Uribe replied in an official letter that he accepted Juanes' manager's suggestion.