The series began as a 2.5-minute short pitched by Chris Savino in 2013 for Nickelodeon's Animated Shorts Program, originally about a male rabbit with twenty-five sisters instead of a human family.

Savino chose to make the original short's characters rabbits (and briefly considered mice) because animal-based cartoons face fewer restrictions from standards and practices, allowing for more extreme physical humor than his previous all-human show Kick Buttowski: Suburban Daredevil.

Executive Jenna Boyd advised Savino to make the characters human to improve the pitch's chances, which led him to base the show on his own childhood in a large family and reduce the number of sisters from 25 to 10.

The rabbit-family concept from the original pitch was later reused as Lincoln's dream sequence in the Season 3 episode 'White Hare'.

Many character names are drawn from Savino's real life: five of his sisters inspired Lori, Luan, Lynn, Lana, and Lisa, while Lola and Luna were named after dachshunds owned by Savino and his mother-in-law; Lucy and Lily were names he and his wife had picked for potential daughters, Leni was named after Lennie Small from Of Mice and Men, and Lincoln was named after E Lincoln Avenue, the street where Savino grew up.

The family surname 'Loud' was suggested by Nickelodeon employee Scott Kreamer, giving Savino the idea to make all the siblings' names alliterative, a naming scheme further inspired by writer Karla Sakas Shropshire, who grew up with three siblings whose names all began with K.

The Loud family's pets—Charles, Cliff, Geo, and Walt—are named after cartoonists Charles M. Schulz, Cliff Sterrett, George Herriman, and Walt Kelly, creators of Peanuts, Polly and Her Pals, Krazy Kat, and Pogo, all cited by Savino as major influences on the series.

The fictional town of Royal Woods combines elements of Savino's hometown of Royal Oak, Michigan, and Huntington Woods, the hometown of story editor and later showrunner Michael Rubiner.

To emulate the look of newspaper comic strips he loved as a child, Savino kept the camera at eye level, used a limited color palette with paper-textured backgrounds, gave each character's wardrobe its own signature color, and incorporated comic tropes like fight clouds and onomatopoeic bursts.

Because the show's large cast would have been difficult to animate traditionally, Savino pushed for the series to be produced using Toon Boom Harmony software to ease the animators' workload.

Creator Chris Savino was suspended and then fired from the studio in October 2017 following sexual harassment allegations; the series continued production without him, with Michael Rubiner named executive producer and showrunner.

The characters Howard and Harold McBride, an interracial gay married couple, are the first married gay couple to be featured in a Nicktoon, and their introduction was widely reported as historic and caused a ratings surge.

Kenya's Film Classification Board called for the suspension of The Loud House on pay-TV service DStv, along with other Nickelodeon and Cartoon Network shows, alleging the programs glorified homosexual behavior; it was unclear if the flagged episodes ever aired there.

The fan fiction 'The Loud House: Revamped', written from 2017 to 2024, reached 16 million words by 2022 and over 30 million upon completion, with The Spectator Australia claiming it to be the longest fiction work in the history of the world.