His father, Clark Hayes, operated the Hayes Hotel in Stannards and was also involved in oil production. George Hayes grew up in Stannards and attended Stannards School. He played semiprofessional baseball while in high school. He ran away from home in 1902, at 17, joined a stock company, apparently traveled for a time with a circus, and became a successful vaudevillian.

Hayes married Olive E. Ireland, the daughter of a New Jersey glass finisher, on March 4, 1914. She joined him in vaudeville, performing under the name Dorothy Earle (not to be confused with film Actress and Writer Dorothy Earle). Hayes had become so successful that by 1928, at age 43, he was able to retire to a home on Long Island in Baldwin, New York. He lost all his savings the next year in the 1929 stock-market crash. Olive persuaded her husband to try his luck in films, and the couple moved to Los Angeles. They remained together until her death on July 5, 1957. The couple had no children.

From 1935 to 1939, Hayes played the part of Windy Halliday, the sidekick to Hopalong Cassidy (played by william Boyd). In 1939, Hayes left Paramount Pictures in a dispute over his salary and moved to Republic Pictures. Paramount held the rights to the name Windy Halliday, so the nickname Gabby was created for Hayes's character. As Gabby Whitaker, he appeared in more than 40 films between 1939 and 1946, usually with Roy Rogers (44 times), but also with Gene Autry (7) and Wild Bill Elliott (14), often working under the directorship of Joseph Kane (34).

The Western film genre declined in the late 1940s, and Hayes made his last film appearance in The Cariboo Trail (1950). He moved to television and hosted The Gabby Hayes Show, a Western series, from 1950 to 1954 on NBC and, in a new version in 1956, on ABC. He introduced the show, often while whittling on a piece of wood, and would sometimes throw in a tall tale. Halfway through the show, he would say something else, and at the end of the show, also, but he did not appear as an active character in the stories. When the series ended, Hayes retired from show Business. He lent his name to a comic book series and to a children's summer camp in New York.

Following his wife's death on July 5, 1957, Hayes lived in and managed a 10-unit apartment building he owned in North Hollywood, California. At the beginning of 1969, he entered Saint Joseph Hospital in Burbank, California, for treatment of cardiovascular disease. He died there on February 9, 1969, at the age of 83. He was interred in the Forest Lawn–Hollywood Hills Cemetery in Los Angeles.

Homage was paid to Hayes in a different way in the 1974 satirical Western Blazing Saddles. The actor and Director Jack Starrett, credited as Claude Ennis Starrett, Jr., played a Hayes-like character. In keeping with a running joke in the movie, the character is called Gabby Johnson. After Johnson delivers a rousing, though partially unintelligible speech to the townspeople, David Huddleston's character stands up to say, "Now, who can argue with that?!", and proclaims it "authentic frontier gibberish."

Every year in early July, from 1983 through 1989, "Gabby Hayes Days" were celebrated in Wellsville, New York. The event featured a street sale, square dancing, and Hayes look-alike contests for adults and children. This celebration was eventually merged into the mid-July Wellsville Balloon Rally and gradually disappeared. A street is also named after him in Wellsville, Gabby Hayes Lane.

The famous Manhattan restaurant Danny's Hideaway, at 151 East 45th Street, called one of its main dining areas the Gabby Hayes Room in honor of the friendship between the owner, Dante "Danny" Stradella, and Hayes.