The band was formed in Los Angeles, California during the punk rock movement. The original lineup consisted of Dinah Cancer on vocals, Paul Cutler on guitar, Rob Ritter (also known as Rob Graves of The Bags) on bass, and Don Bolles (of The Germs) on drums. The band evolved out of an industrial music band called Vox Pop, who recorded two singles and played around the Los Angeles area, specifically in the punk institution the Masque. Vox Pop contained all of the members of 45 Grave as well as others, such as Jeff Dahl. Vox Pop continued to coexist with 45 Grave until early 1981. The band's name, despite rumors to the contrary, was lifted from a button.

In 1980, 45 Grave recorded their first song, "Riboflavin Flavored, Non-Carbonated, Poly-Unsaturated Blood", included on the LAFMS (Los Angeles Free Music Society) art rock compilation album, "Darker Skratcher". The song is a cover version of the cult favorite originally done by "Don Hinson And The Rigamorticians" on their 1964 album release "Monster Dance Party". Don Hinson at the time was a popular radio personality in Las Vegas, Nevada (and later for 20 years in Los Angeles, California). Mr. Hinson recorded the song in the wake of Bobby "Boris" Pickett's 1962 novelty song hit "Monster Mash" hoping to emulate the latter song's success and have an international hit record. Both "Monster Mash" and the Don Hinson original recording of "Riboflavin Flavored, Non-Carbonated, Poly-Unsaturated Blood" were produced by noted novelty song record producer Gary S. Paxton of Skip & Flip. The 45 Grave recording went on to achieve cult status and is a signature song during the bands live shows. 45 Grave members appeared as extras in Blade Runner directed by Ridley Scott.

Early on, the band were playing The Consumers songs that Cutler had written, with lyrics changed to fit Cancer's singing style. They then wrote the songs that would be released on their first 7", "Black Cross", which featured Pat Smear of The Germs on guitar, and a fast paced punk song called "Party Time".

Despite never achieving major success, 45 Grave are recognised as being one of the first American Gothic bands, pre-dating the formation of Christian Death. Allmusic guide cites them as a top artist in the Goth rock genre.

45 Grave's musical style is punk rock with a darker edge/horror movie aesthetic, and hence is representative of the genre deathrock/horror-punk. Keyboards are used to create an electric organ sound which adds to the 'spooky' atmosphere of many songs. High-pitched female vocals are usually used but the whole band provide backing vocals and occasionally lead vocals. The band also has a connection to surf rock which manifests in their album "Sleep in Safety" as the instrumental "Surf Bat". In the vein of horror punk artists, the band's appearance draws from horror films, in particular Italian zombie flicks, to create a camp, gothic aesthetic. However, the band's lyrical themes don't often draw inspiration from horror films, instead adopting a tongue-in-cheek manner.

In 1984 a slowed down version of "Party Time" was featured on the soundtrack to the film Return of the Living Dead along with tracks by bands such as TSOL and The Cramps. Another track, "Evil", was featured on MTV. The band then recorded their one studio album to date, "Sleep In Safety" and then in 1985, broke up.

The band reformed in 1989 for a brief tour, which was recorded and released as "Only The Good Die Young". However when Ritter died in 1990, from an accidental drug overdose, the band broke up yet again.

In 2004, to commemorate its 25th anniversary, 45 Grave reformed with a new lineup, Dinah Cancer being the single remaining member from previous incarnations. Dinah Cancer posted on her MySpace blog, "I'm building this to keep the spirit of 45 Grave alive, introduce its magic to new fans, and as a personal commemorative of my best memories being the driving force and front person of 45 Grave. This is a part of my life that indeed changed me forever." One of the touring members involved in this line-up was Rikk Agnew, formerly of Christian Death.