McGuire was born in Oklahoma City, Oklahoma, and moved to California in early childhood, when he was two years old. After working as a commercial fisherman, and then going on to become a journeyman pipe fitter, McGuire got a job singing in a bar. In 1961, he released his first single called "The Tree", which was not a hit.
He formed a duo with Barry Kane (d. 2013) called Barry & Barry. The new duo folk act performed their own brand of original folk arrangements—noticeably impressive melodies laced with rich harmonies—at The Ice House, a small folk club in Pasadena, CA. before moving on to The Troubadour in Hollywood in the spring of 1962. At The Troubadour they both joined The New Christy Minstrels, a large folk group performing there, and McGuire sang lead vocals on their novelty single "Three Wheels on My Wagon".
They continued to perform their separate duo act there as well as performing with The New Christy Minstrels. Under Horizon Records, they cut their first and only album as Barry & Barry called: Here And Now which contained songs such as "Gold Wedding Ring", "Land Of Odin", the single "Another Man", "Summer's Over", "You Know My Name", "Bull 'Gine Run", and "Far Side Of The Hill". It also included "If I Had A Hammer". released three months after the release of the same song by folk trio Peter, Paul and Mary.
In 1963, McGuire along with Randy Sparks (the founder of The New Christy Minstrels) co-wrote, and sang lead vocal on, the Christys' first and biggest hit single: "Green, Green." He left the Christys in January 1965, after recording the album Cowboys and Indians; however, on the 1965 album Chim Chim Cher-ee, he sang only on the title cut.
As a folk rock solo singer in the 1960s, he was best known for his hits "Eve of Destruction" and "Sins of a Family", both written by P.F. Sloan. Barry's other chart successes were "Child of Our Times" and "Cloudy Summer Afternoon (Raindrops)" (penned by Travis Edmonson of the 1960s folk-duo, Bud & Travis). "Eve of Destruction" sold over one million copies, and was awarded a gold disc.
McGuire's The Eve of Destruction, peaked at No. 37 on the Billboard 200 albums chart during the week ending September 25, 1965. That same week the single of that name went to No. 1 on both the Cashbox and Billboard Hot 100 charts. McGuire was never again to break into the Top 40. The song knocked Help! by The Beatles out of the top spot on the chart. According to McGuire, "Eve of Destruction" was recorded in one take on a Thursday morning (from words scrawled on a crumpled piece of paper) and then he got a call from the record company at 7:00 the next Monday morning, telling him to turn on the radio—his song was playing. The recording includes an "ahhh" where McGuire could not read the words. The Temptations referenced McGuire's song "Eve of Destruction" in their song "Ball of Confusion (That's What the World Is Today)".
The album This Precious Time was released in 1966, his second with Dunhill Records. It includes a version of "California Dreamin'" with The Mamas & the Papas singing backing vocals. McGuire is mentioned several times in The Mamas & the Papas hit, "Creeque Alley". Frank Zappa wrote McGuire's name in the sleeve of his Freak Out! album (1966) as one of his musical influences.
McGuire appeared in the 1967 movie The President's Analyst with James Coburn as the character "Old Wrangler" (leader of a band which completely comprised the Los Angeles group Clear Light, who were between lead vocalists) and in Werewolves on Wheels in 1971. He also starred for a year in the Broadway musical Hair in 1968. Barry also appeared in an episode of "Matt Dillon".
McGuire became a born-again Christian in 1971 after a brief encounter with evangelist Arthur Blessitt in October 1970. In 1973, he joined the Myrrh label and released the album Seeds. This album is also notable for the backing vocals provided by the family trio that would become known as the 2nd Chapter of Acts. In 1974, McGuire released his second Jesus music album Lighten Up, which included a remake of "Eve of Destruction". He toured with 2nd Chapter of Acts and "a band called David" and in 1975 this collaborative effort resulted in the double live album To the Bride.
In 1976, he left Myrrh, joining former Myrrh executive Billy Ray Hearn's new label, Sparrow Records. He recorded seven albums on Sparrow, the best known of which is Cosmic Cowboy, released in 1978. That year he also released a top-selling children's album Bullfrogs and Butterflies (part of the Agapeland series) for Sparrow's subsidiary label, Birdwing.
In 1978, he toured England, Scotland, and Wales with the Jimmy Owens' musical "The Witness", in which he played the part of the apostle Peter, a part he also played on the studio recording of "The Witness".
In the 1980s, McGuire left the music industry, and settled for a time in New Zealand with his wife, Mari. He returned to the United States in the 1990s, teaming up with Terry Talbot and recording as Talbot McGuire. The duo released four albums between 1996 and 2000.
In 1990, he published a novel co-written with Logan White. A paperback, In the Midst of Wolves, told a story about a group of bikers who come to know God. He did a brief stint with The New Mamas and the Papas in 1997–1998.
As of 2006, he takes engagements which include a few songs and talks on a mixture of topics, by both McGuire and his wife. The McGuires reside in Fresno, California, but also spend part of every year in New Zealand.
On March 12, 2008, McGuire appeared on the Australian music comedy/game show, Spicks and Specks, performing an updated version of "Eve of Destruction", with new lines such as, "You're old enough to kill/ you just started voting" and "... can live for ten years in space". The reference to "Red China" was also removed. In 2009 McGuire released "Eve 2012" where the text had been greatly modified to reflect contemporary problems (mostly environmental problems) rather than the problems of the 1960s.
In 2008, McGuire teamed up with former member of the Byrds, John York, for a live tour called "Trippin' the '60s", which McGuire describes as "taking the songs and the truth that was in those songs from the 1960s and bringing them into the present moment...It's not a cover pack, it's us singing songs that we sung with a lot of our friends that aren't around anymore to sing them."1962: Barry Here and Now
1963: The Barry McGuire Album
1965: Eve of Destruction
1965: This Precious Time
1967: The World's Last Private Citizen
1971: McGuire and the Doctor
1974: Lighten Up
1975: To the Bride
1975: Eve of Destruction (Star Power)
1976: C'mon Along
1976: Anyone But Jesus
1976: Jubilation Two
1977: Have You Heard
1978: Cosmic Cowboy
1979: Inside Out
1980: Best of Barry McGuire
1981: Finer Than Gold
1991: Let's Tend God's Earth
1995: When Dinosaurs Walked the Earth
1997: Ancient Garden
1999: Frost and Fire
2000: Eve of Destruction (20 Inspirational Classics)