Originally released on the band's 1985 album, Theatre of Pain, the song was accompanied by a music video which documented the band's undertakings over the course of a concert, or several concerts. Some of the original video was shot in Houston, Texas live at The Summit during the 1985 Theatre of Pain tour. They performed the song twice that night apparently to get more video footage. "Home Sweet Home" was released & remixed twice: once for the original promotion for the single in 1985. A radio only promo 12" with the remix was sent to stations, but not released commercially until the 1988 Japan-only EPRaw Tracks. The song was remixed again in 1991 and had some instruments overdubbed. Now called "Home Sweet Home '91", it was released as a single with a new video and included on the Decade of Decadence compilation. The song is often referred to as a power ballad, and its success was a prelude to similar marketing formula for other hair bands in the late 1980s. The song ranks number twelve on VH1's chart of the greatest power ballads of all time. Drummer Tommy Lee re-recorded the song for Season 4 of the TV series Californication, and has a cameo in "Lights, Camera, Asshole" performing the song on piano in a bar at the end of the episode. Also, the third episode in the show's fourth season was named after this song.
The original release of "Home Sweet Home" charted at number 89 on the Billboard Hot 100, and "Home Sweet Home '91" peaked at number 37 on the same chart in 1992. To date, "Home Sweet Home '91" is the last Mötley Crüe song to chart in the American Billboard Top 40.
The video (directed by Wayne Isham and guest-starring actor Michael Berryman) depicts each band member receiving a phone call home, and replying "I'm on my way!", Vince Neil on a beach, Mick Mars on a throne in a haunted house, Nikki Sixx at a bar, and Tommy Lee at a wild party. The piano intro begins as a tour bus driving by is shown. The rest of the video shows the band pre-concert and performing on stage, shot at The Summit in Houston, Texas (concert footage) and Reunion Arena in Dallas, Texas (exterior). The video is notable for its long stay on top of the MTV daily request chart, lasting over three months until MTV invoked the unwritten "Crue Rule", dropping videos from eligibility on their request line after thirty days. The end of the video shows the same tour bus from the beginning with the words "Rockin 'N' Rollin".
The song was re-recorded by Linkin Park vocalist Chester Bennington on co-lead vocals along with Mötley Crüe in the wake of Hurricane Katrina. The music video for the song shows videos of Katrina rescues, along with a performance from the band.
30 Foot Fall included a cover version of the song as a bonus track on their album Ever Revolving, Never Evolving.
Tommy Lee performed the song on piano when he guest starred as a singer on the TV series Californication at the end of the episode of "Lights, Camera, Asshole". This version also appears on the show's Season 4 soundtrack.
In 2016, Disney and Play-a-Sound published a musical sound button book based on the 2016 animated feature film Finding Dory, titled "Swim Along with Me". On the module, there is a button with a picture of Dory on the bottom of the module. When pressed, an instrumental of the Home Sweet Home plays. The lyrics of the song are printed on the last page, using the phrase "be it ever so humble, there's no place like home".