Sullivan was originally a newspaper sportswriter and theater columnist for the New York Daily News. His column concentrated on Broadway shows and gossip. He also did show business news broadcasts on radio. Sullivan continued writing for The News throughout his broadcasting career.

In 1948, the CBS network hired Sullivan to do a weekly Sunday night TV variety show, Toast of the Town, which later became The Ed Sullivan Show. The show was broadcast from CBS Studio 50 on Broadway in New York City, which in 1967 was renamed the Ed Sullivan Theater (and is now the home of The Late Show with David Letterman).

Sullivan himself had little acting ability; his mannerisms on camera were somewhat awkward and often caricatured by comedians who called him "Old Stone Face," owing to his deadpan delivery. Columnist Harriet Van Horne alleged that "he got where he is not by having a personality, but by having no personality; he is the commonest common denominator." According to the crazyabouttv.com website, Sullivan replied with a short note:

Dear Miss Van Horne, You bitch. Sincerely, Ed Sullivan Somehow, Sullivan still seemed to fit the show; he appeared to the audience as an average guy who brought the great acts of show business to their home televisions. Sullivan had a healthy sense of humor about himself and permitted- even encouraged- impersonators such as John Byner and Rich Little to imitate him on his show.

In the 1950s and 1960s, Sullivan was a respected starmaker because of the number of performers that became household names after appearing on the show. He had a knack for identifying and promoting top talent and paid a great deal of money to secure that talent for his show.

There was another side to him: he could be very quick to take offense if he felt that he had been crossed and could hold a grudge for a long time.

Jackie Mason, Bo Diddley, and The Doors became intimately familiar with Sullivan's negative side. The Doors were banned in 1967 after they were asked to remove the lyric "Girl, we couldn't get much higher" from their song "Light My Fire" (CBS censors believed it was too overt a reference to drug use) and sang the song with the lyrics intact. Jim Morrison is reported to have said "***k you." to Ed's stagemanager and nephew, Bob Precht. (The Rolling Stones were a different story; they were forced to change the chorus of "Let's Spend the Night Together" to an incomprehensible mumble, or by some accounts "Let's Spend Some Time Together," rather than accept censorship.) Jackie Mason was banned from the series in 1962, when Sullivan gestured that he should wrap things up and Sullivan believed Mason replied on live television with the finger.

On November 20, 1955, Bo Diddley was asked by Sullivan to sing Tennessee Ernie Ford's hit "Sixteen Tons". Come air time, Diddley sang his #2 hit song, "Bo Diddley". He, too, was banned from the show.

In 1961. Sullivan was asked by CBS to fill in for an ailing Red Skelton on The Red Skelton Show. He performed some of Skelton's characters successfully. One character was renamed "Eddie the Freeloader" (normally "Freddie the Freeloader).

In August of 1956 he was injured in an automobile accident that occurred near his country home in Southbury, Connecticut and had to take a medical leave from the show missing the September 8 appearance of Elvis Presley on his show (something he earlier stated never would happen but he later changed his mind). The fact he had to play catch up to featuring such a star on his show made him determined to get the next big sensation first. In 1964, he achieved that with the first live American appearance of The Beatles. The Beatles first appearance, on February 9, 1964, was the most-watched program in TV history to that point, and remains one of the most-watched TV programs of all time.

Sullivan paid for the funeral of dancer Bill 'Bojangles' Robinson out of his own pocket. He also defied pressure to exclude African American musicians from appearing on his show.

By 1971, the show was no longer in television's top 20. New CBS executives, who wanted to attract younger viewers, canceled the show along with virtually all of the network's oldest shows. Sullivan was so upset and angry he refused to do a final show, although he did come back to CBS for several TV specials and a 25th anniversary show in 1973. One year later, the man known as "Old Stone Face" died of cancer at the age of 73.

He was married to Sylvia Weinstein from April 28, 1930 until her death on March 16, 1973. They had one child.

He has a star on the Hollywood Walk of Fame at 6101 Hollywood Blvd.