The band's debut album The Big Come Up had been tremendously successful for an independent rock band and Thickfreakness further increased their profile. It continues The Black Keys' tradition of raw, heavy blues-influenced garage rock. Thickfreakness is known in Japan as Inazuma Rockin' Blues, with "inazuma" meaning "flash of lightning".
Songs such as "Set You Free" won the pair some mainstream success as being featured in the soundtrack of the 2003 film School of Rock. Heavy comparisons to another American blues-influenced garage rock duo, The White Stripes, were often made in the music media.
Most of the album was recorded in 14 hours in Patrick Carney's basement on an early 1980s Tascam 388 8-track recorder. The liner notes claim this is Carney's "patented recording technique called 'medium fidelity'". The result is an older sounding sound. The song "Midnight in Her Eyes" is one of the few Black Keys songs that used a bass guitar; Dan Auerbach dubbed a bassline by playing a Guild SG-style bass through a guitar amp into the song. Part of "Set You Free" was recorded by Jeff Saltzman.