Marc Brown was initially reluctant to adapt his Arthur books into a TV series because he didn't want to give up creative control of his characters, but he agreed after executive producer Carol Greenwald assured him the show would encourage children to read and visit libraries.

Marc Brown's son Tolon, for whom Brown originally invented the character of Arthur the Aardvark in a bedtime story, later became the show's executive director, and other elements like a moving company named 'Tolon Moving' and items labeled 'Eliza' reference Brown's children.

The setting of Elwood City draws on Marc Brown's hometown of Erie, Pennsylvania, with the show's Mill Creek Mall referencing the real Millcreek Mall and the character Mr. Ratburn being based on a middle-school algebra teacher Brown had at Westlake Middle School.

Most of the show's animation and voice acting was produced in Montreal by CINAR, before production relocated to Toronto in 2004 after CINAR was rebranded as Cookie Jar Entertainment; animation outsourcing was also done in South Korea and Hong Kong.

The only segments of the show filmed outside Canada were the live-action 'A Word from Us Kids' interstitials, shot at elementary schools in the Boston area.

In 1999, CINAR's chairman and president were investigated for tax fraud after secretly investing $122 million into Bahamian bank accounts, but Arthur itself was not implicated since it was publicly known as an American co-production.

The reggae-style theme song 'Believe in Yourself' was performed by Ziggy Marley and the Melody Makers, and the Backstreet Boys later covered it for the TV special Arthur: It's Only Rock 'n' Roll.

The song 'Crazy Bus,' written and performed by then-head writer Joe Fallon, served as an alternate anthem of the show until Fallon left after season 4, after which it was retired and even mocked in dialogue by D.W. in a later special.

In May 2019, Alabama Public Television refused to air the episode 'Mr. Ratburn and the Special Someone' depicting the wedding of Arthur's teacher to another man, having previously also declined to broadcast a 2005 spin-off episode featuring a child with two mothers.

The show frequently parodies pop culture franchises such as South Park, The Sopranos, Star Wars, The Matrix, Titanic, and Harry Potter, which has helped it build a dedicated cult following among older audiences.

In 2016, stills from the episode 'Arthur's Big Hit' showing Arthur's clenched fist became widely used as internet memes on Black Twitter, prompting a public comment from WGBH acknowledging the memes 'in good fun' while expressing disappointment at a few in poor taste.