Patrick McHale first envisioned the concept in 2004 with a scarier, more adventure-based storyline, and pitched it to Cartoon Network in 2006 under the title Tome of the Unknown.

The original pitch followed two brothers named Walter and Gregory who signed a Faustian deal with a devil named Old Scratch and journeyed across the Land of the In-Between to find pages of a book of forgotten stories.

McHale abandoned the original concept centered on chapters of a mystical tome, and the series was retitled Over the Garden Wall after the network asked him to develop a pilot following his work on Flapjack and Adventure Time.

McHale originally envisioned eighteen chapters for the series, but the episode count was reduced to ten to fit budget and time constraints.

Early drafts of the show's pitch bible included a skinless witch character, a villain who carved dice from the bones of kidnapped children, and a running plot where Wirt and Greg would be transformed into animals, with Greg becoming a duck and Wirt becoming either a bear or a dog.

Production was largely based in Burbank, California, but many artists worked remotely from other U.S. cities, including storyboard artists located in New York and Chicago, which McHale found particularly challenging given the idiosyncratic nature of the production.

The show's animation was outsourced to the South Korean studio Digital eMation.

The series' digital backgrounds were designed to resemble brunaille paintings, evoking 19th- and 20th-century Americana.

The show's art was inspired by a variety of sources, including the 1890s McLoughlin Brothers board game Game of Frog Pond, Gustave Doré's illustrations for Don Quixote, old illustrations for Hans Christian Andersen's 'The Tinderbox', John Tenniel's Cheshire Cat illustration from Alice's Adventures in Wonderland, and the 'Dogville Comedies' short films.

McHale also drew on chromolithography, vintage Halloween postcards, magic lantern slides, and photographs of New England foliage to shape the show's visual style.

For the music, McHale drew inspiration from classic American opera singing, and Elijah Wood said that if the show were a record, it would be played on a phonograph.

A cassette tape titled 'For Sara', modeled after a prop cassette seen in the series, was released by Mondo in September 2015, featuring poetry read by Elijah Wood as Wirt and songs from the show.

The series won an Emmy Award for Outstanding Animated Program in 2015 and holds a 94% approval rating on Rotten Tomatoes based on 16 reviews.

A three-minute stop motion short film produced by Aardman Animations was released on November 3, 2024 to mark the series' 10th anniversary, reuniting several cast and crew members including McHale, Elijah Wood, and Melanie Lynskey.

The show has become closely associated with autumn, with fans rewatching it annually in October and November, and outlets like Vox and The Week describing it as a seasonal viewing tradition.