Their music incorporates experimentalism with sludgy riffs, drop-tuned guitars and elements of psychedelic rock. The group was established in 2001 by the former members of Damad, with the addition of guitar player Laura Pleasants who is from North Carolina. The band has since undergone line up changes; the remaining original members are Phillip Cope and Laura Pleasants. In 2006, the band added two drummers (Carl McGinley of Unpersons, from Savannah, and Jeff Porter). Eric Hernandez (of Capsule, from Miami) joined in 2008 to replace Porter. The dual drum tracks are often panned strongly to the right and left.

Kylesa is a metal group that borrows elements of punk, psychedelic rock, stoner rock, sludge metal, and indie rock. They have two different singers and formed in Savannah in 2001, taking their name from "kilesa mara", a Buddhist term denoting delusory mental states.

Guitarist and singer Phillip Cope, bassist Brian Duke and drummer Christian Depken were former members of the Savannah sludge metal act Damad, which released two albums in the '90s. Philip Cope has been described as the Savannah "metal scene's godfather." Damad changed their name to Kylesa in 2001 with the addition of Laura Pleasants, a native of North Carolina who attended the Savannah College of Art and Design.

After recording the majority of their first record (S/T on Prank) in May 2001, Kylesa played their first show with Mastodon and Cream Abdul Babar in Savannah, Georgia on June 2, 2001. On June 6, 2001, Brian Duke died from an epileptic seizure during the course of the night. The band decided to finish the recording in Brian's honor, wrote and recorded two more songs (where local bass player and friend Michael Redmond stepped in and played bass). The self-titled record was released about one year later on Prank Records when artwork by Pushead was completed. Prior to the full LP, a single limited 7" was released on Prank also with Pushead art. The Pushead-designed Band Logo from these releases has been used on all the bands merchandise and releases ever since.

Replacing Duke with bassist and singer Corey Barhorst, the band wrote and recorded a split 7" with Memento Mori, on Hyperrealist, and a split full length with Cream Abdul Babar from Florida, on At A Loss Recordings. These records came out immediately following the release on Prank, although they were recorded much later, The long wait for artwork by Pushead delaying the release of the S/T LP. More singles and a placeholder EP, 2004's No Ending 110 Degree Heat Index followed right before Depken left the group.

Kylesa signed with the independent metal label Prosthetic Records and released their second proper album, To Walk a Middle Course, in 2005 with drummer Brandon Baltzley.

Following the release of that album, Baltzley left the group, replaced by a pair of drummers, Jeff Porter and Carl McGinley. Kylesa's third album, Time Will Fuse Its Worth, was released on Halloween 2006. Eric Hernandez replaced Porter and appears on Static Tensions, released in 2009.

Journalist David Peisner of Spin described them as "dark psych-metal titans," practicing an "aggressive [sound], but with a hazy, stoner vibe that suggests a strange amalgamation of Black Sabbath, Black Flag, and early Pink Floyd." In 2010 they signed to the Season of Mist records label to release the album Spiral Shadow on October 26 that year. A rarities compilation album titled From the Vaults, Vol. 1 was released later that year.

Their latest album, Ultraviolet, was released through Season of Mist on May 28, 2013. The record is darker lyrically and sonically than previous works, containing more vocals from singer/guitarist Laura Pleasants. The band embarked on a full North America headlining tour to promote the release.