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Released in 1986, it was the first single from the band's fourth album, Fore!. The song spent three weeks at number one on the US Billboard Hot 100, becoming the band's second number-one hit on the chart. Internationally, the song became the band's second top-20 hit in the United Kingdom, reaching number 12 on the UK Singles Chart, and peaked within the top 10 in Australia, Canada, Iceland, South Africa, and New Zealand.

The group was under a lot of pressure to deliver a leadoff hit single, but they struggled for months. Their manager, Bob Brown, made a personal appeal to Huey Lewis & the News guitarist Chris Hayes, asking him to come up with something. According to Hayes in a Rolling Stone interview, he responding by taking a six-pack of beer into the studio and emerging three hours later with the music for "Stuck With You." Lewis added the lyrics, and they had their single.

The Huey Lewis & the News official site used to have a "Question Of The Week" section where Lewis would answer questions from fans. In 2013, he answer one asking who "Stuck With You" is about. Huey's reply: "None of your business! But, I will tell you, that although my songs are often inspired by real things, in fact, usually inspired by real life, they aren't always literal, and I always 'embellish'... but, I will also reveal that the person who inspired 'Stuck With You' didn't really like the song all that much.

The music video was filmed in the Bahamas in July 1986 and features Keely Shaye Smith. The island that Lewis and Smith wind up on is a small island about ten miles from Paradise Island in Nassau. The video was filmed on land, on water, underwater, and from the air. The band, the crew and all the extras used in the island barbecue scene had to stay on a barge moored off the island so that they wouldn't be seen. The costumes were designed by Bambi Breakstone who designed the costumes for the 2nd season of Miami Vice (1985/1986).

The video was directed by Edd Griles, who had previously directed the band's videos for "The Heart of Rock & Roll" and "If This Is It", as well as Cyndi Lauper's "Girls Just Want to Have Fun", "She Bop" and "Time After Time".