Penrod was born in Taylor, Texas, and grew up in Hobbs, New Mexico, where his father, Rev. Joseph Loren "Joe" Penrod, was the lead pastor of Temple Baptist Church, and his mother is Barbara Josie Penrod (née, Gray). He graduated from Hobbs High School. During his high school years Penrod recorded his first album, singing all four parts.
Penrod is a graduate of Liberty University. Starting in the 1980s, he worked as a studio singer, backing up voices such as Carman, Steve Green, Amy Grant, Michael W. Smith, Garth Brooks, Shania Twain, James Ingram, and Phillips, Craig & Dean. He was also a member of the Christ Church Choir (as was another future Gaither Vocal Band member, Jonathan Pierce). During his years in the studio, he met Bill Gaither for the first time. He also made regular appearances on TNN's Music City Tonight as a background singer in the mid-1990s.
After accepting the position with the Gaither Vocal Band in 1994, Penrod became internationally known for his powerful vocals and broad singing range. He has performed in Gaither Homecoming concerts all over the U.S. and Canada, as well as in Europe, Australia, and Africa. In 1998, he performed a duet with the Cathedral Quartet's lead singer Glen Payne on their Farewell Celebration video.
Penrod performed for the grand opening of Jerry Falwell's new Thomas Road Baptist Church new 6,000 seat sanctuary.
His album, The Best of Guy Penrod, reached No. 92 on the Billboard 200 on August 6, 2005. The DVD release was certified platinum by the RIAA.
The Gaither Vocal Band's 2006 release was entitled Give It Away, followed by Lovin' Life in 2008. Penrod won a Grammy Award for his work on the "Lovin Life" project.
In a press release on January 13, 2009, Bill Gaither announced that Penrod would be leaving the Gaither Vocal Band and starting a solo career.
In August 2009, Penrod released his debut solo album, Breathe Deep, on the Servant Records label. Produced by veteran country music producer and studio musician Brent Rowan, the album consists of positive country music with Christian undertones.
Guy was inducted into the Texas Gospel Music Hall of Fame in 2011.
Penrod's sophomore solo album Hymns debuted at No. 1 on the Nielsen SoundScan Southern gospel retail chart, became the top-selling southern gospel album of 2012, and was also one of the year’s top-selling gospel recordings in Cracker Barrel Old Country Store® nationwide. Hymns sold over 100,000 units.
In 2012, Penrod became the new host of Gospel Music Showcase, a popular Daystar Television Network program that focuses on southern gospel music. It can be seen every Saturday. The show has been awarded an Emmy.
Penrod won "Soloist of the Year" from the National Quartet Convention in 2013.
Penrod released his third solo project titled Worship in May 2014.
In September 2014, Penrod released his first solo Christmas project entitled "Christmas." It became the No. 2 album in Cracker Barrel stores with 30,000 units sold, second only to Blake Shelton.
Also in 2014, Guy was inducted into the Gospel Music Hall of Fame alongside the Gaither Vocal Band.
Penrod released his first solo DVD entitled Live: Hymns & Worship in January 2016. The Project was filmed at Thomas Road Baptist Church. The release debuted at No. 1 on the Billboard chart for music videos sold upon its release. The album debuted at #2 on the "Billboard" chart for contemporary Christian music.
Penrod was a featured performer at the Faith Freedom & Future Inaugural Ball hosted by the Family Research Council, following the January 2017 inauguration of U.S. President Donald Trump in Washington, DC.
In March 2017, Penrod returned with an album entitled Classics. The album was a new solo recording of popular songs he performed during his tenure with the Gaither Vocal Band.
Guy has often appeared on the stage of the "Grand Ole Opry" as a guest artist.
Penrod and his wife, Angie (Clark), have eight children—seven boys and a girl (the youngest)... All their children are home schooled.1995: Southern Classics, Vol. 21997: Loving God & Loving Each Other1998: Still The Greatest Story Ever Told1999: God Is Good2000: I Do Believe2002: Everything Good2003: A Cappella2004: The Best Of The GVB2006: Give It Away2007: Together, feat. Ernie Haase & Signature Sound2008: Lovin' Life2008: Christmas Gaither Vocal Band Style2009: Reunion, Vol. 1 & 2