The title track from the Honeycutters' debut album is a bittersweet remembrance of childhood. The narrator recalls sneaking cigarettes and swigs of rum and running wild with her best friend. The band's frontwoman, Amanda Anne Platt, grew up near New York City but moved to Asheville, North Carolina, where she wrote "Irene." She told Songfacts: "I had not been in Asheville long and I was coming up against the fact that I'm really not a kid anymore. I've moved to this other city and I'm making my own way now and remembering things about my childhood. That chorus felt like a good solidifier of all the things that I was feeling."
The chorus borrows the refrain "Goodnight, Irene" from the folk standard of the same name and calls back to Platt's memories of listening to her dad's band rehearse. "They would practice at our house from time to time and I would always want to hang out with the boys and not go to bed," she explained. "When it was time for me to go bed they would sing 'Goodnight, Irene.'"