Served as one of the influences in the development of the Hanna-Barbara cartoon Scooby Doo, Where Are You! (1969). In Scooby-Doo, the character of Fred Jones was based on Dobie Gillis; Velma Dinkley on Zelda Gilroy; Daphne Blake on Thalia Menninger, and Norville "Shaggy" Rogers on Maynard G. Krebs.

The pilot for this series was the first professional acting job for Bob Denver, who had been a grade school teacher and postal worker before joining the cast. Denver's sister was a casting agent's secretary, and had his name added to the audition candidates for the role of Maynard G. Krebs.

A pilot for a "Zelda" spin-off starring Sheila James was produced in 1962, but was scrapped after James T. Aubrey, then head of CBS, rejected this. James was told by producer/director Rod Amateau that Aubrey found Zelda "too butch", a critique that deeply worried James, then a closeted lesbian. James, under her real name of Sheila Kuehl, went into law and politics after acting parts dried up, eventually becoming the first openly gay person elected to the California State Assembly and a California State Senator.

Bob Denver was drafted during the production of the series' fourth produced episode, "The Big Sandwich". Maynard was therefore written out of the series with the episode "Maynard's Farewell to the Troops", and Michael J. Pollard was cast as Maynard's cousin Jerome Krebs, who would assume Maynard's role in future episodes. However, Denver failed his Army physical and was rejected "4F" by the draft board. After shooting two episodes with Pollard, this was decided to rehire Denver and write Maynard back into the series. Pollard had signed a "play or pay" contract, and was paid for all 30 episodes he had been signed for upon his dismissal.

In every episode save for one ("Take Me to Your Leader" from Season Two), Dobie breaks the fourth wall and directly addresses the audience via monologues on the plot of the week's episode, seated or standing in front of a replica of Rodin's statue "The Thinker". These monologues were typically used as framing devices at the beginning and end of each episode and during scene transitions. In the earliest produced episodes, Dobie would be seen sitting in the same pose as the statue.

The "G" in Maynard G. Krebs stands for Walter, Maynard's aunt. Maynard explained that the "G" is because his mother "didn't spell too good".

The character Dr. Imogene Burkhart was played by Jean Byron, who was born Imogene Burkhart.

Dwayne Hickman later reported not being fond of his on-screen love interest, Tuesday Weld, who left the series after the first season (save for two return appearances in later seasons) to pursue other roles.

Max Shulman and his writers had little knowledge of beatniks, a term used by outsiders to refer to devotees of the Beat Generation philosophy, so Bob Denver visited Los Angeles area coffee shops and hipster hangouts in order to help create Maynard G. Krebs.

Dobie's father Herbert T. Gillis had a catchphrase during Season One whenever he found himself stymied or frustrated by Dobie: "I gotta kill that boy, I just gotta!". The sponsors disapproved of the running gag, and required the producers to both discontinue its use and soften somewhat the hard edges of Herbert T. Gillis.

Actors William Schallert and Jean Byron, who often appeared on the series playing various teachers of Dobie in high school and college, went on to play Patty Duke's parents in the later sitcom, The Patty Duke Show (1963).

To differentiate Dobie Gillis from Chuck McDonald, the character Dwayne Hickman played on The Bob Cummings Show (1955), Max Shulman and Fox required Hickman to dye his dark brown hair blond. Their concern was that the sponsors would feel audiences would confuse Dobie with Chuck, a character on a different series with different sponsors. Continually bleaching his hair caused Hickman to suffer hair loss and blisters on his scalp, and after appealing to the producers, he was allowed to stop bleaching his hair after the first season.

The teacher's name is an inside joke, of sorts. Pomfritt, as in "Pomme Frites" is another name for "Chips", as in the beloved teacher in the film Goodbye, Mr. Chips (1939).

Zelda knew Dobie loved her because she wrinkled up her nose and Dobie involuntarily did this back in spite of himself.

The occupation of Dobie's father was different in each of the short stories upon which the series was based. In the series, his job was "locked in" as a grocer.

In multiple episodes, characters mention they have seen or are going to see a movie entitled "The Monster That Devoured Cleveland".

Warren Beatty, cast as Dobie's nemesis Milton Armitage, did not enjoy working on the series. He left the series midway through the first season to return to stage work, and Steve Franken was cast as Chatsworth Osbourne Jr., a replacement character who appeared throughout the remainder of the series. Doris Packer, who had played Milton's mother Mrs. Armitage, was retained, with her character becoming Mrs. Chatsworth Osbourne Sr.

Despite being cast as teens, Dwayne Hickman was 24 and Bob Denver was 23 when they filmed the pilot in mid-1958.

Whenever Maynard hears the word "work", this startles him and he responds by saying "work!" in a frightened high-pitched voice, while jumping slightly. Even when Maynard says "work" within a normal sentence himself, this startles him and he repeats the word in the frightened manner.

The role of Davey Gillis, Dobie Gillis' older brother in three Season One episodes, was played by Darryl Hickman, Dwayne Hickman's real-life older brother.

The song "Love is a Many Splendored Thing" is often used as background music when Dobie is feeling romantic because 20th Century Fox, the producers of the series, owned the rights to the song and did not have to pay for its use.

Some of Maynard's mixed-up malaprops: Should be Guillotine = he says gelatin Eureka = Europa Hermit = helmet Gargoyle = argyle OCS = COD Casanova = Casablanca Coma = comma Barbarians = barbers Atomic = platonic Survival of the fittest = fattest Benedict Arnold = Arnold Benedict

During Season One and the first half of Season Two, the "Thinker" set is also an actual location in the context of the show, a section of the Central City park. After Dobie joins the Army in season two, the park set is replaced with a "void" set featuring only Dobie and the statue of "The Thinker". In seasons three and four, Dobie would employ props, usually large photos of the principal players, in his monologues.

Cashing in on the series' popularity, a line of young men's leisure apparel, "Dobie Gillis Originals", was launched. The tags featured humorous annotations such as "Like, lifted from Maynard".

Maynard called Dobie "Good buddy".

Chatsworth called Dobie "Dobie-do".

Dobie has two "rich boy" nemesis on the series, first Milton Armitage who is then followed by Chatsworth Osbourne Jr. Series creator Max Shulman was raised in the Selby-Dale neighborhood of St. Paul Minnesota. If one is traveling west on Selby Avenue, one will first cross Milton Street which is followed by Chatsworth Street.

Maynard called Zelda "Small girl".