The song is best known in a recording by The Everly Brothers, issued by Cadence Records as catalog number 1337. The Everly Brothers record reached number one on the Billboard Pop chart and the Cash Box Best Selling Records chart, despite having been banned from Boston radio stations for lyrics that, at the time, were considered suggestive, according to a 1986 interview with Don Everly. "Wake Up Little Susie" also spent seven weeks atop the Billboard country chart and got to number two on the UK Singles Chart. The song was ranked at #318 on the Rolling Stone magazine's list of The 500 Greatest Songs of All Time.
In an appearance on The Oprah Winfrey Show during the 2000 U.S. presidential election, then-Governor George W. Bush named "Wake Up Little Susie" as his favorite song. "Wake Up Little Susie" was the first single filmmaker David Lynch bought.
The song is written from the point of view of a high school boy to his girlfriend, Susie. In the song, the two go out on a date, only to fall asleep during the movie. They do not wake up until 4 o'clock in the morning, well after her 10 o'clock curfew. They then contemplate the reactions of her parents and their friends.
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Simon and Garfunkel have cited the Everly Brothers as strong influences on their own music. Their live version of "Wake Up Little Susie," recorded in the duo's concert in New York's Central Park on September 19, 1981, reached #27 on the Billboard Hot 100 in 1982, and is the duo's last Top 40 hit.
During Simon & Garfunkel's "Old Friends" tour in 2003-2004, they performed this song and others in a segment with the Everly Brothers, who toured in support.