On September 9, 1956, Elvis Presley made his first appearance on The Ed Sullivan Show. On October 28 of the same year, Elvis made his second appearance on the show. He made his third and final appearance on January 6, 1957.

The Beatles made their U.S. television debut on the Ed Sullivan Show on February 9, 1964. That broadcast drew approximately 73 million viewers, which at the time was a record for American television. They made appearances on three consecutive Sundays that month.

In a time that offered few opportunities for African Americans on U.S. TV, The Supremes appeared almost 20 times on Sullivan's show. Other Black entertainers on the show included: Frankie Lymon, James Brown, Ray Charles, Nat King Cole, Bo Diddley, The 5th Dimension, The Four Tops, Aretha Franklin, The Jackson 5, Gladys Knight & the Pips, Little Anthony & The Imperials, The Miracles, Sly & the Family Stone, The Temptations, Martha Reeves & The Vandellas, Tina Turner and Stevie Wonder.

The Doors were well known for their appearance on the Sullivan show on September 17, 1967. The network censors required that Jim Morrison change the lyrics to their hit single Light My Fire by altering the line, "Girl, we couldn't get much higher." However, Morrison sang the original line on live television with no delay!

For the Rolling Stones' January 15, 1967 appearance, the network censors required them to change the title of their "Let's Spend the Night Together" to "Let's spend some time together". They caved and made the change.

Currently this is the place where The Late Show With David Letterman Show is filmed.