After their split, Mayer continued to play local clubs, refining his skills and gaining a following. After his appearance at the 2001 South by Southwest Festival, he was signed to Aware Records, and then Columbia Records, which released his first EP, Inside Wants Out. His following two full-length albums—Room for Squares (2001) and Heavier Things (2003)—did well commercially, achieving multi-platinum status. In 2003, he won the Grammy Award for Best Male Pop Vocal Performance for the single “Your Body Is a Wonderland”.

By 2005, Mayer had moved away from the acoustic music that characterized his early records, and begun performing the blues and rock music that had originally influenced him as a musician. He collaborated with blues artists such as B. B. King, Buddy Guy, and Eric Clapton. Forming the John Mayer Trio, he released a live album in 2005 called Try!, and his third studio album Continuum in 2006. Both albums received critical acclaim, and Continuum earned Mayer a 2007 Grammy Award for Best Pop Vocal Album. He also won Best Male Pop Vocal Performance for “Waiting on the World to Change”. That album was followed by Battle Studies in 2009, a return to pop, with a Battle Studies World Tour.