Frontman Win Butler told The A.V. Club why he chose the title 'Neon Bible' for the album: "I just jotted it down in my notebook and kept coming back to it. The song was very much off-the-cuff, written in one night and recorded the next day. Lyrically, there's a lot of stuff dealing with religion and culture, which I'm really interested in. It's an image that I kept coming back to that really felt like it was the title of the record. And everyone else in the band agreed."
John Kennedy Toole's novels were rejected during his lifetime, and after suffering from depression due in part to these failures, he committed suicide in 1969 at the age of 31. Some years later, his mother brought the manuscript of A Confederacy of Dunces to the attention of novelist Walker Percy, who managed to get the book into print. The novel attracted much attention in the literary world and in 1981, Toole was posthumously awarded the Pulitzer Prize for Fiction.
Win Butler first discovered Toole as a teenager whilst boarding at an exclusive school in New Hampshire. Neon Bible was later named after Toole's first book, which was published posthumously, after A Confederacy of Dunces had made him famous.
Phil Oakey recorded his vocals for "Don't You Want Me" in the studio bathroom. The recording was disrupted by guitarist Jo Callis reaching through an open window from outside to repeatedly flush one of the toilets.