Born Brenda Gail Webb in Paintsville, Kentucky, Gayle began performing and recording during the early 1970s.

Her fourth album, We Must Believe in Magic (released in 1977) brought her to a wide audience. Fuelled by the worldwide hit single "Don't It Make My Brown Eyes Blue" (written by Richard Leigh), which reached number one on the U.S. country music charts, but also was a number two pop single, the album became a best seller, the first by a female Country Artist to reach Gold Album status. She won a Grammy Award for Best Female Country Vocal Performance for the single. In 1977 and 1978 she was chosen the Country Music Association's "Female Vocalist of the Year." She also toured with Kenny Rogers in Britain. Gayle has also been selling out the crowds world-wide on her own as well, in addition to a trip to China with Bob Hope where she became the first person to tape a performance on the Great Wall of China. She has appeared in her own specials on CBS, to critical acclaim and very high ratings, which led to her "Christmas in Sweden" special, as well.

She continued to achieve success on the country charts, with such songs as "Why Have You Left the One You Left Me For", and achieved several hits on the pop charts including "Talking in Your Sleep", "Half the Way", and a duet with Eddie Rabbitt, "You and I", all three of which made the Pop Top 20 and Adult Contemporary Top 10, creating the "crossover" which broke down barriers, and paving the way for others that followed in her footsteps, such as Shania Twain and Faith Hill. Her world-wide appeal, and versatility as a songstress, led to a string of 18 number one hit songs. Her trademark song, "Don't It Make My Brown Eyes Blue," was awarded as one of the top ten most played songs of the 20th Century. Her album True Love was the first non-"greatest hits" album to yield four number one singles.

With many of her hits being songs about heartbreak, a contemporary Shoe comic strip featured a muscular, vengeful character saying "I want to find the guy who's doing all those terrible things to Crystal Gayle!"

Crystal Gayle and Tom Waits recorded the soundtrack to the movie One from the Heart in 1982 (see also One from the Heart (album)).

Gayle continues to record and perform, packing halls from Louisville to Leningrad. In 1987, she guest-starred on the soap opera Another World; she played herself and was menaced by a serial killer known as the "Sin Stalker". She sang a duet with Gary Morris both on the show and at the 1987 Daytime Emmy Awards. From October 1987 until March 1996, her duet was the theme song for the serial.

One of Gayle's most cherished awards came in October 2000, when the Cherokee Nation bestowed upon her their highest award, the Cherokee Medal of Honor. On June 9, 2005, she took the stage at the Grand Ole Opry in Nashville, Tennessee for a live reprise of her cross-over smash hit, "You and I," a duet she had recorded with the late Eddie Rabbitt. That song had been named the number 7 all-time best/favorite Country Music Duet during a countdown and concert that listed the "Top 100 Greatest Country Duets" of all time.

Gayle's admitted "heartbeat" is her family. She married her high school sweetheart, Bill Gatzimos, shortly after graduating high school. The couple has two children, Catherine and Cris, and one grandson, Elijah. Gayle's family resides in Nashville, where she also has her own specialty store, "Crystal's for Fine Gifts and Jewelry."

A new Crystal Gayle in Concert DVD was taped in Nashville on June 9, 2005, and was scheduled for a fall 2005 release date.

Gayle remains extremely popular with not only Country Music fans, and maintains a very hectic and full concert tour schedule, with dates already booked well into 2007.

Gayle is noted for her long hair, which cascades down to the floor when displayed at full length.