The lyrics are sung from the point of view of a man whose former girlfriend, named Sue, was extremely unfaithful. He warns all potential lovers to avoid her at all costs, as Sue "runs around" with every guy she meets and never settles down with any man in particular. He advises "Now people let me put you wise, Sue goes out with other guys" and suggests that potential suitors should 'keep away from Runaround Sue'. Dion stated in his autobiography "The Wanderer" that although his wife's name was Susan, Runaround Sue had nothing to do with her. However, during a 1990 interview with his wife on the Oprah Winfrey Show, they presented the story that the song was indeed about her.
"Runaround Sue" was covered by Leif Garrett in 1977. The song was the second of four releases from his debut album, all of which became U.S. chart hits. All four songs were covers of major hits from 1959 to 1963, including Dion's two biggest hits. Of the four, "Runaround Sue" was the most successful for Garrett. In early 1978, his version reached number 13 on Billboard and number 18 on Cash Box. The song also reached number 15 in Canada.