Gill was born in Norman, Oklahoma. His father, J. Stanley Gill, who played in a country music band part time, encouraged Gill to pursue a musical career. At the encouragement of his father, Gill learned to play several instruments, including the banjo and guitar, before he started high school at Oklahoma City's Northwest Classen High School. He first played with a teenage band called Bluegrass Revue in the late 1970s. While in high school, he performed with "Mountain Smoke," a bluegrass band that once opened for Pure Prairie League. After he graduated, he played in a number of bluegrass bands, including Ricky Skaggs' "Boone Creek"; later, he became a member of Rodney Crowell's road band, The Cherry Bombs.

Gill debuted on the national scene with the country rock band Pure Prairie League in 1979, appearing on that band's album Can't Hold Back. Gill is the lead singer on their hit song "Let Me Love You Tonight" (1980). Gill appeared on two subsequent albums along with then-wife Janis Gill before signing as a solo with RCA Records in 1983. In 1989, he switched to MCA Records where he recorded his breakthrough hit "When I Call Your Name."

Gill hosted the CMA Awards every year from 1992–2003. In 2004 he received a Grammy Award for Best Male Country Vocal Performance. In 1997, he was inducted into the Western Performers Hall of Fame at the National Cowboy & Western Heritage Museum in Oklahoma City, Oklahoma. Dire Straits leader Mark Knopfler, a fan of Gill's music, had asked Gill to join the band full time. Gill turned down the invitation, but did sing backup on one song ("The Bug") from Dire Straits' album On Every Street. Gill has also sung duets with numerous artists, including Dolly Parton("I Will Always Love You"), Alison Krauss and Union Station ("That's All"), Reba McEntire ("Oklahoma Swing," "The HeartWon't Lie," "It Just Has to Be That Way,""These Broken Heart"), Amy Grant("House of Love"), and Barbra Streisand("If You Ever Leave Me"). More recently, Vince and Sheryl Crow sang harmony vocals on the Brooks & Dunn 2006 hit "Building Bridges". In 2006, Gill released "These Days," a 4-CD set of 43 new recordings featuring a range of musical styles: traditional country, ballads, contemporary, and acoustic/bluegrass. Guest performers included Sheryl Crow, Emmylou Harris, Diana Krall Trisha Yearwood, Michael McDonald, Bonnie Raitt, Leann Rimes Gretchen Wilson, Amy Grant and Lee Ann Womack among others.

In 2007, Gill along with Mel Tillis and Ralph Emery were inducted into the Country Music Hall of Fame and in 2008, he won his 19th Grammy for Best Country Album.

Gill married country singer Janis Oliver of Sweethearts of the Rodeo fame, in 1980. The couple has one daughter, Jennifer Jerene Gill, born May 5, 1982. Vince and Janis separated in the mid-1990s and eventually divorced in June 1998. Vince married Christian/pop singer Amy Grantin March 2000. They have one daughter, Corrina Grant Gill, born March 12, 2001.