His chance came in 1960, when Sheldon Leonard, the producer of "The Danny Thomas Show," developed an idea that would exploit the actor's homespun image: Griffith would play Andy Taylor, the sheriff in a series set in a mythical North Carolina town called Mayberry.
"The Andy Griffith Show"made its debut that fall with Ronny Howard as the widowed sheriff's young son, Opie, and Frances Bavier as matronly Aunt Bee. The series quickly became one of the decade's most popular shows and made Griffith one of television's most beloved stars.
Griffith, 86, died Tuesday at his home on North Carolina's Roanoke Island, according to a family statement read by Dare County Sheriff Doug Doughtie. No cause was given, but Griffith had a heart attack and underwent quadruple bypass surgery in 2000.
A former North Carolina high school music teacher, Griffith launched his career as an entertainer in the early 1950s by writing and performing comic monologues for civic clubs that he delivered in an exaggerated Southern drawl that he once described as "sounding like three yards out on a Carolina swamp."
Before the end of the decade, he was a star known for his Tony-nominated Broadway performance as a hayseed recruit in "No Time for Sergeants" and his film debut as an Arkansas vagabond who becomes a power-hungry TV sensation in director Elia Kazan's dark drama "A Face in the Crowd."
His portrayal of Sheriff Andy Taylor on "The Andy Griffith Show," which aired on CBS from 1960 to 1968, gave him a place in television history as one of the medium's most memorable characters, alongside such iconic TV fathers as Robert Young of "Father Knows Best" and Lorne Greene of "Bonanza."
Griffith scored a second triumph on series television starring in "Matlock," the legal drama that ran from 1986 to 1995 on NBC and ABC. He played Benjamin L. Matlock, a Harvard-educated lawyer with a down-home sensibility.
As an actor, he learned early on to play to his strengths.
"Any time I try to play anything that doesn't come natural, I'm just plain bad," he once told TV Guide.
As Sheriff Taylor, his most famous role, he was just plain good.
He made his debut as the avuncular sheriff in early 1960 during a guest spot on CBS' "The Danny Thomas Show," in which Sheriff Taylor picked up nightclub entertainer Danny for speeding through Mayberry on his way to Miami.
"The Andy Griffith Show" earned a spot on the network's fall lineup and high ratings for eight seasons.
Comic actor Don Knotts, who had a supporting role alongside Griffith in the Broadway and film versions of "No Time for Sergeants," had seen the "Danny Thomas Show" episode and called to suggest that Andy Taylor should have a deputy.
The addition of Knotts as the incompetent but full-of-bravado Barney Fife quickly shifted the balance of the show.
"I was supposed to have been the comic, the funny one," Griffith told The Times in 1993. The series, he said, "might not have lasted even half a season that way, but when Don came on I realized by the second episode Don should be funny and I should play straight to him."
The unflappable Andy and the all-too-excitable Barney became one of television's greatest comedy duos.
The show's laughs came not from the characters telling jokes back and forth but typically, as in real life, out of ordinary conversations.
One of Griffith's favorite exchanges with Knotts came in an episode in which Barney had saved $300 to buy a car.
Barney: The last big buy I made was my mom's and dad's anniversary present.