Hayes was born in Wellsville, New York and did not come from a cowboy background. In fact, he did not know how to ride a horse until he was in his forties and had to learn for movie roles. Hayes' early show business career included working in the circus, in vaudeville, on stage, and playing semi-professional baseball.

Hayes married Olive Dorothy Ireland in 1914. They remained together until her death in 1957. The couple had no children.

Hayes' film career began in 1923 with his appearance in the silent film Why Women Marry. In his early career, Hayes was cast in a variety of roles, including villains, and occasionally played two roles in a single film. Hayes briefly retired in the 1920's but lost most of his money in the 1929 stock market crash and had to return to acting. He fortunately found a niche in the growing genre of western films, many of which were series with recurring characters. Ironically, Hayes would admit he had never been a big fan of westerns.

Hayes, in real life an intelligent, well groomed, and articulate man, was cast as a grizzled codger who uttered phrases like "consarn it", "yer durn tootin", "durn persnickety female", and "young whipper snapper". Hayes played the part of Windy Halliday, the sidekick to Hopalong Cassidy (William Boyd), from 1935 to 1939. 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 a new nickname was created for Hayes' character; Gabby. As Gabby Whitaker, Hayes appeared in over forty pictures between 1939 and 1946, usually with Roy Rogers but also with Gene Autry or Bill Elliot. Hayes also was repeatedly cast as a sidekick to western icons Randolph Scott and John Wayne. In fact, Wayne and Hayes made numerous films together in the very early '30s with Hayes playing "straight" pre-sidekick roles, and sometimes even the villain. Hayes became a popular performer and consistently appeared among the ten favorite actors in polls taken of movie-goers of the period.

The western film genre declined in the late 1940's and Hayes made his last film appearance in The Cariboo Trail (1950). He moved to television and hosted The Gabby Hayes Show, a children's western series, from 1950 to 1954. When the series ended he retired from show business.

For his contribution to radio, Gabby Hayes has a star on the Hollywood Walk of Fame at 6427 Hollywood Blvd. and a second star at 1724 Vine Street for his contribution to the television industry. In 2000, he was posthumously inducted into the Western Performers Hall of Fame at the National Cowboy & Western Heritage Museum in Oklahoma City, Oklahoma.

Gabby Hayes died in Burbank, California in 1969 and 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. A lookalike actor named Claude Ennis Starrett, Jr. played a Gabby Hayes-like character. In keeping with one running joke in the movie, the character was called Gabby Johnson. After he delivered a rousing, though largely unintelligible, speech to the townspeople ("You get back here you pious candy-ass sidewinder. Ain't no way that nobody is gonna' to leave this town. Hell, I was born here, an' I was raished here, an' dad gum it, I am gonna die here, an no sidewindin bushwackin, hornswaglin, cracker croaker is gonna rouin me biscuit cutter."), David Huddleston's character proclaimed, "Now, who can argue with that?!" and described it as "authentic frontier gibberish."