Its centerpiece was a monologue that usually recounted humorous stories about things that had supposedly happened to him, as well as stories allegedly about his real-life wife, Alice (nicknamed "Spooky Old Alice" and played by actress Jeff Donnell). Gobel's hesitant, almost shy delivery and penchant for tangled digressions were the chief sources of comedy, more important than the actual content of the stories he told. His monologues popularized several catch phrases, notably "Well then there now" (repeated by James Dean in Rebel Without a Cause), "Well, I'll be a dirty bird" and "You don't hardly get those any more."
Gobel described himself as "Lonesome George," and the nickname stuck for the rest of his career. The TV show typically included a segment in which Gobel appeared with a guitar, started to sing, then got sidetracked into a story, with the song always left unfinished after fitful starts and stops. He had a special version of the Gibson L-5 archtop guitar built, featuring diminished dimensions of neck scale and body depth, befitting his own small stature; a series of several dozen of this "L-5CT" or "George Gobel" model was produced in the late 1950s and early 1960s. He also played harmonica.
In 1957 three B-52 Stratofortress bombers made the first nonstop round-the-world flight by turbojet aircraft. One of the aircraft was christened "Lonesome George." The crew appeared on George Gobel's prime-time television show and recounted their mission which took them 45 hours, and 19 minutes. Lonesome George, the tortoise, is also named after Gobel.
Gobel was a guest on various TV programs, including Johnny Carson's The Tonight Show. In an often-replayed segment from a 1969 episode of The Tonight Show, Gobel followed Bob Hope and Dean Martin, walking onstage with a plastic cup with an unidentified drink. Gobel ribbed Carson about coming on last and having to follow those major TV stars. He quipped to Carson, "Did you ever get the feeling that the world was a tuxedo and you were a pair of brown shoes?" After the laughter died down, Carson asked Gobel about his career in World War II as a fighter pilot. Gobel feigned bewilderment at why people laugh when he says that he spent the WWII in Oklahoma, pointing out that no Japanese plane ever got past Tulsa. Gobel also began to get some unexpected laughs, being unaware that Dean Martin had begun flicking his cigarette ashes into Gobel's drink. Observing all of this, Carson finally asked rhetorically, "At what point did I lose control of the show?"
Gobel also became a regular panelist on the TV show Hollywood Squares. In the early 1980s, Gobel played Otis Harper, Jr., the mayor of Harper Valley in the television series based on the film Harper Valley PTA.
When ratings soared on The George Gobel Show (rated in the top ten of 1954-55), Paramount promoted Gobel as their new comedy star, casting him as the lead in The Birds and the Bees (1956), a remake of The Lady Eve (1941). However, Gobel's TV success did not translate to the big screen. The film performed so poorly at the box office that release was delayed on his second Paramount movie, I Married a Woman, filmed in 1956 but not released until 1958. Although scripted by Goodman Ace, it also resulted in disappointing ticket sales, and Gobel's career as a Paramount movie star came to an abrupt end. He settled into an endless succession of TV guest star appearances and did not return to movie screens until years later as a character actor in Joan Rivers' Rabbit Test (1978), followed by The Day It Came to Earth (1979) and Ellie (1984). He made nine TV movies during the 1970s and 1980s.