The group first formed in 1985 when Liam Ó Maonlaí and Fiachna Ó Braonáin, who had known each other as children in an Irish-speaking school, Coláiste Eoin in Booterstown, Dublin, began performing as street musicians, also known as buskers, on the streets of Dublin as "The Incomparable Benzini Brothers".

They renamed the group "Hothouse Flowers" (the name was suggested by singer Maria Doyle Kennedy during a brain-storming by band-members and friends in the Trinity College Arts Block café) and began writing songs and performing throughout Ireland.

In January 1992, the group appeared (as themselves) in an episode of the popular BBC drama series Lovejoy, entitled No Strings.

In 1992, Hothouse Flowers joined Def Leppard – the combined group going by the name The Acoustic Hippies From Hell – to record three songs ("From the Inside", a cover of the Rolling Stones' "You Can't Always Get What You Want", and a cover of Jimi Hendrix's "Little Wing") that were included as B-sides on Def Leppard's single "Have You Ever Needed Someone So Bad", from their album Adrenalize.

[1] Though it received good reviews and achieved some chart success in Australia and Ireland, worldwide sales were disappointing.

The band also participated in the Another Roadside Attraction tour in Canada that year, and collaborated with The Tragically Hip, Crash Vegas, Midnight Oil and Daniel Lanois on the one-off single "Land" to protest forest clearcutting in British Columbia.

By early 1994, Ó Maonlaí had decided that the group was suffering from physical, mental and creative exhaustion, and he called for a year-long sabbatical.

The year-long break turned into several years, as the band members recouped their energy and experienced changes in their personal lives, including divorces, marriages, the birth of children and the death of Ó Maonlaí's father.

O'Toole and Ó Braonáin spent some of their time off from the Hothouse Flowers recording and touring with Michelle Shocked.

Ó Maonlaí worked with Tim Finn and Andy White (see ALT (band)), while also studying traditional Irish music.

In 2007, Ó Braonáin appeared on Belinda Carlisle's album Voila, singing a duet with her on a cover of "Bonnie and Clyde".

Ó Braonáin and Clarke have also collaborated with a former member of The Pogues in the group Pre-Nup, who have opened some shows in America for Hothouse Flowers.

During an interview on "The Imelda May Show" in Ireland, the band confirmed they were working on a new album, tentatively scheduled for release in early 2016.

[7] The band played a live version of their cover "I Can See Clearly Now" on the premiere episode of Amazon Prime's The Grand Tour first made available to stream in November 2016.

Former band member, saxophone player Leo Barnes, died of an apparent brain hemorrhage in April, 2022.