"Crazy", their first single, based on samples of the song "Nel Cimitero Di Tucson" (1968) by Gianfranco Reverberi, gained some of its popularity due to its use on primetime BBC Radio 1 DJ Zane Lowe's television advert, and it was also made Record of the Week by Ken Bruce of BBC Radio 2. Some of the popularity is also due to the performance of the song at The 2006 MTV Movie Awards, where the band performed in Star Wars costumes -- including the garb of Rebel Alliance pilots, Imperial officers, Stormtroopers, Chewbacca, Jango Fett, Obi-Wan, with Cee-Lo singing as an unmasked Darth Vader. It was released as a single on April 3, 2006, preceded by its release as digital download and 12" vinyl single in March 2006. On 2 April 2006, it became the first ever UK number one single based on download sales alone.

In an interview with Observer Music Monthly, Danger Mouse denied that the band's name is a reference to former basketball player Charles Barkley, saying "Nope. It's just like everything else on this record. There was no conscious decision about stuff."

The duo made their debut performance at the Coachella Valley Music and Arts Festival on April 30, 2006,[3] but their first concert, hosted by Myspace.com, part of the Secret Show series, took place at The Roxy Theatre in Los Angeles on April 28, 2006. They are set to perform at Lollapalooza 2006 in Chicago and the Austin City Limits Music Festival in Austin. Their U.S. television debut was made on May 25, 2006 during Late Night with Conan O'Brien. The duo also appeared on the prestigious BBC TV music show, Later with Jools Holland, on May 19, 2006, and on the June 12, 2006 edition of The Tonight Show with Jay Leno.

"Crazy" is the first single to top the UK singles chart for nine weeks consecutively since 1994 when Wet Wet Wet's "Love Is All Around" was number one for fifteen weeks (the last song to spend exactly nine weeks on top was "Two Tribes" by Frankie Goes To Hollywood in 1984). It has also equalled the Queen 1975 classic "Bohemian Rhapsody", which also topped the UK singles chart for nine weeks. Crazy is also the longest number-one on the UK Official Download Chart with its stay lasting eleven consecutive weeks. Gnarls Barkley announced that as the record had spent its ninth week at number one, it was to be deleted as a vinyl/CD listing from May 28, 2006 so people will "remember the song fondly and not get sick of it".