Cleveland-born Wilcox was inspired to play guitar after watching a fellow student play in a stairwell at Antioch College in Yellow Springs, OH. Transferring to Warren Wilson College in Asheville, NC, in 1981, Wilcox began taking music seriously. Although he took four lessons with a classical guitarist, Wilcox developed most of his playing technique on his own. In addition to being inspired by Joni Mitchell to play in a variety of tunings, he designed a capo that produced an unusual sound by leaving one or more strings unaltered.

Wilcox strengthened his skills as a performer through regular appearances at an Asheville night club called McDibbs. His debut album, The Nightshift Watchman, was released in 1987 on his own label, Song of the Woods, and reissued in 1996 by Koch International; it featured scaled-down arrangements and launched Wilcox's career as a touring musician. After performing at the Bluebird Cafe in Nashville, Wilcox signed with A&M in 1989. His first release on the label, How Did You Find Me Here, sold over 100,000 copies by word of mouth. Wilcox subsequently recorded two other studio albums for the label -- Home Again in 1991 and Big Horizon in 1994. In 1991, the label released a six-song CD, Mostly Live: An Authorized Bootleg. East Asheville Hardware, Wilcox's first album after being dropped by A&M, featured live recordings of previously unreleased tunes including a version of Chuck Brodsky's satirical song "Blow 'Em Away."

His contract with A&M ended after four albums in 1994, but Wilcox has continued to share his love of music and his explorations of personal growth. His 1997 album Turning Point recorded in the log cabin studio in the woods behind his home, represented a shift to a more controlled approach to music, while his February 1999 release, Underneath, continued to focus on his vocals and guitar playing despite the additional instrumentation of electric guitars, keyboards, and rhythm section. Although his albums have featured diverse arrangements, Wilcox continues to perform in concert as a soloist. In August 2000, What You Whispered was released. A best-of collection followed the next year, released during his successful national tour. Due to his popularity, the demand for a live album became too great and he offered Live Songs and Stories in the summer of 2002. Into the Mystery appeared in 2003, followed by a joint effort with Nance Pettit, Out Beyond Ideas, in 2005, Vista in 2006 and Airstream in 2008.