Born in Antigua, he was interested in music from an early age but later decided to become a rural schoolteacher. He also played basketball for the Guatemalan national team, but continued to play guitar and write songs in his spare time. After realizing that music was vocation, he moved to Mexico City; once there, he began looking for a record contract and played at many student festivals.

Arjona finally found a contract through PolyGram, but the label attempted to market him as a Latin lover type on his debut album, Dejame Decir Que Te Amo (Let Me Say I Love You). Predictably, the album failed, and Arjona spent the next five years teaching and occasionally writing songs recorded by other artists. He moved to Buenos Aires, began playing again, and soon returned to the recording sphere with material more suited to his experiences as a protest singer, namely "Jesus Verbo No Sustantivo," a controversial song about his experiences at a Catholic school as a child. It gained him a contract with Sony, which released many of his most popular albums, including 1992's Animal Nocturno. His next two albums, 1994's Historias and 1996's Si el Norte Fuera el Sur, were not only popular but critics' favorites as well.

Galería Caribe, which appeared in 2000, became Arjona's first number one album on the Top Latin Albums chart, and 2002's Santo Pecado won him a Latin Grammy Award. Adentro, released in late 2005, was a landmark in Arjona's catalog; it marked the first of several contributions by Puerto Rican producer and songwriter Tommy Torres, and won Arjona another Latin Grammy. 5to Piso followed in 2008, bolstered by the help of Torres plus a massive hit single in "Como Duele." Poquita Ropa arrived two years later, in 2010, with Arjona adopting more of a stripped-down approach. Released in 2011, Independiente featured a poppier sound and style that made the album a success, and the lead single "El Amor" a big hit. In typical fashion, Arjona switched gears again for 2014's Viaje, a singer/songwriter album through and through, driven by life on the road and depression brought on by the death of his mother. ~ John Bush