A significant figure in the development of the Southwest psychedelic rock movement, Lopez has established a number of noted bands including Mostly Bears and Xixa, and played with internationally recognized artists Calexico, Giant Sand, KT Tunstall, and Nouvelle Vague.

The son of Pima Community College basketball coach Michael Lopez and Sandy Kondrat,[3] he showed an early aptitude for music and began playing guitar at the age of 12 while attending Roskruge Bilingual K-8 Magnet School.

Reflecting his views on the desert city, he noted in a 2012 interview with Best New Bands, "It’s a desperate environment filled with dwellers and survivalists.

"[9] In 2005, Lopez, with musical partners Geoffrey Hidalgo and Nick Wantland, launched the indie rock band Mostly Bears.

Lopez was part of an important group of 21st-century emerging musicians within Tucson in the early 2010s, including Sergio Mendoza, Salvador Duran, and Gabriel Sullivan,[13] who were creating a new indie rock sound tied to the cultural roots of southern Arizona, Northern Mexico, and the geography of the place.

In response to the 2011 Tucson shooting, which injured congresswomen Gabby Giffords, Lopez joined with other noted performers included Neko Case and Jimmy Eat World to create a compilation record Luz de Vida to raise funds for those impacted.

[14] In 2011, Lopez sang backing vocals on the song "Windows Are Rolled Down" on Amos Lee's album Mission Bell.

European tastemaker Music Express called Lopez: "the missing link between Devendra Banhart and Roy Orbison" and gave "Ultra" 4.5 out of 5 stars.

In addition to his solo work, during this period, Lopez played in Howe Gelb's band Giant Sand and had inclusion on the album "Tucson".

Lopez's songs have been used in film and tv scores including Frank and Cindy starring Renee Russo and Oliver Platt in 2015, the Netflix original series October Faction in 2020, CBS's border drama Coyote in 2021,[22] and Amazon Prime Video's series Night Sky starring Sissy Spacek and J.K. Simmons in 2022.

In 2019, XIXA released their second EP "The Code.” Since 2016, the band has toured extensively in the US and Europe, playing numerous music festivals including South by Southwest in Austin, Texas,[26] Vive Latino in Mexico City, and Lowlands in Utrecht, Netherlands.

In May 2018, Lopez announced he would be playing with internationally recognized band Calexico as lead guitarist and backing vocalist, touring North America, Australia and Europe.