His debut album Signs and Signifiers was released in 2010 on Hi-STYLE Records. The album was given a major-label release by Rounder Records on April 17, 2012, debuting at number one on the Billboard Heatseekers Albums chart and number 161 on the Billboard 200 the week of June 2, 2012. It also reached number 47 on the Billboard Rock Albums chart.

He studied visual arts in college, earning a Master of Fine Arts from the University of Tulsa, and later worked as an art and technology teacher. After deciding to pursue music more seriously, McPherson sent a demo to Jimmy Sutton of the small independent record label Hi-STYLE Records, which specialized in roots music. Sutton agreed to produce McPherson’s debut album: this became 2010’s Signs and Signifiers. On 19 November 2012, Rolling Stone labelled McPherson an “Artist to Watch” in a 3½ star (out of 5) review of Signs and Signifiers after its wider release through Rounder Records.

The single “Your Love (All That I’m Missing)”, from the album Signs and Signifiers, was released by Rounder/Hi-STYLE in the UK on June 18, 2012.

In October 2015, JD McPherson and band appeared (in animated form) as musical guests performing a new and original song “Crazy Horse” for the DreamWorks animated TV series, The Mr. Peabody & Sherman Show on Netflix.

McPherson’s second album, Let the Good Times Roll, was released on February 10, 2015.

JD McPherson’s third album Undivided Heart and Soul was released on October 6, 2017. The song “Under the Spell of City Lights” is featured in the soundtrack of MLB The Show 18.

JD McPherson’s fourth album Socks, a holiday album, was released on November 2, 2018. In Matt Collar’s AllMusic review, he asserted that the album is “a jubilantly rockin’ production, rife with humor and the Oklahoma-born singer’s knack for old-school ’50s R&B.”