It became Simon's sole number-one hit as a solo artist on the Billboard Hot 100 in the United States and was his highest charting song in France, where it peaked at number two.

The single was certified gold by the Recording Industry Association of America (RIAA), denoting sales of more than one million copies.

"[1] In 2023, Simon appeared on The Howard Stern Show and stated that the he wrote the chorus lyrics while teaching his son Harper how to rhyme.

Ramone overheard Gadd practicing and asked him to incorporate these ideas into the verses, which was ultimately retained in the final mix.

[7] Contemporary reviews of "50 Ways to Leave Your Lover" were positive, with Billboard called it an "excellent song" that has "very clever lyrics" and an "easy to listen to melody.

"[9] Record World said that the song "finds Simon aided by a crack team of session men and the unmistakable vocals of Phoebe Snow.