Mathis comes from a prolific musical family and started learning the fundamentals of classical music when he was four years old. Before picking up the bass guitar at eleven, he spent time studying piano, cello, and voice. His early influences included Beethoven, The Beach Boys, Led Zeppelin, Cliff Burton of Metallica, Michael Jackson, and Jimi Hendrix. When Mathis was fifteen he performed Vivaldi's "Mandolin Concerto in D" on mandolin with members of the Tulsa Philharmonic. At sixteen he attended the Interlochen Center for the Arts near Traverse City, Michigan, where he was the top-ranked bassist in the program. While at the academy he developed a love of jazz music, and began transcribing and memorizing the music of Charlie Parker, John Coltrane, Charles Mingus, Thelonious Monk, Miles Davis, Duke Ellington, Louis Armstrong and his Hot Five, and bass virtuoso, Jaco Pastorius. In 1994, Mathis met Brian Haas and a group of like-minded Tulsa musicians, who together created the Jacob Fred Jazz Odyssey. Originally an octet, the band toured six years before becoming the piano-bass-drums trio for which it became known. Mathis continued to tour and record with JFJO through 2008. Mathis' unique style and tone has been described as "talking bass." In a feature article in Bass Player in September, 2002, noted music author Bill Milkowski writes: "No other electric bass player around today has been as successful at incorporating mind-blowing and mondo-effects into a personal voice on the instrument. The charismatic Mathis is freed up to soar into the high register and wail with impunity on his heavy effected bass guitar because Haas is holding down the basslines on the Rhodes." In 2005–2006, Mathis toured with the Steve Kimock Band, which featured Steve Kimock on guitar and lap steel guitar, Robert Walter on Hammond B3 organ and Rhodes piano, and Rodney Holmes on drums. In 2006, Mathis united with pianist Marco Benevento and drummers Matt Chamberlain and Andrew Barr to form the Marco Benevento Trio. He has appeared on three releases with the Marco Benevento Trio and continues to tour with the group. The trio appeared at New York City's famed Carnegie Hall in June, 2009. In late 2007, Mathis joined the San Francisco rock band Tea Leaf Green. In 2008, he split time between TLG and JFJO. He appears on the Tea Leaf Green's 2008 release Raise Up The Tent and tours as a member of the band. In 2008, Mathis produced Jacob Fred Jazz Odyssey's "Winterwood". Shortly before the album's release in January, 2009, Mathis announced his departure from JFJO, citing a desire to pursue his other musical endeavors. Chris Combs and Matt Hayes joined Haas and Josh Raymer to form the new JFJO lineup. In 2009 Mathis became an original member of 7 Walkers, a band led by Grateful Dead drummer Bill Kreutzmann. He recorded on their self-titled debut album that was released on November 2, 2010. He left the band in 2010 due to touring commitments with Tea Leaf Green and was replaced by George Porter Jr.. Mathis performed with the Rhythm Devils for their 2011 tour. In 2014 he joined Billy Kreutzmann's new band Billy & the Kids as well as The Golden Gate Wingmen with John Kadlecik. He left Tea Leaf Green in 2016 to focus on his other projects.