The band's earliest albums were noted for their noise rock influences, though their sound evolved by the early 2000s with the releases of Misery is a Butterfly (2004) and 23 (2007), which both incorporated elements of dream pop, shoegaze and other genres.

Amedeo and Simone Pace were born in Milan, Italy,[6] and grew up in Montreal (Saint-Léonard), but later moved to Boston to study jazz.

Blonde Redhead formed in New York in 1993 after Amedeo and Simone met Kazu Makino, a film student at the time, through mutual friends.

[12] The band enlisted the help of Vern Rumsey of Unwound, who filled the role of guest bassist, while the subsequent albums have featured the Icelandic musician Skúli Sverrisson.

In 2000 Picciotto also co-produced Melody of Certain Damaged Lemons with Ryan Hadlock, an album about the relationship between Makino and Amedeo Pace.

[15] The four-year delay between Melody of Certain Damaged Lemons and Misery Is a Butterfly is attributed to Makino's recovery time after being trampled by a horse.

[21][22] In 2009, Blonde Redhead collaborated with Devestations on "When the Road Runs Out" for the AIDS benefit album Dark Was the Night produced by the Red Hot Organization.

[30] Simone Pace noted about Brown's involvement that "he has so much experience and definitely dictated the direction of the record; the choices of instruments, concept and that it was minimal."

[39] In 2017, the band released the EP 3 O'Clock, which comprises four songs and featured contributions from Eyvind Kang, Michael Leonhart, Sam Owens and Mauro Refosco, among others.

[40] In September 2019, Kazu Makino released her first solo album, Adult Baby, which featured Ryuichi Sakamoto (on piano, field recordings, and "organic instruments"), Ian Chang and Greg Saunier (drums), and Mauro Refosco (percussion).