[3] At Archbishop Carroll High School, Thompson emerged as a standout center, playing in three consecutive City Championship games (1958–60).

In 1959, Carroll All-Mets Thompson, Monk Malloy, George Leftwich and Tom Hoover won over Cardozo 79–52.

Carroll capped off the undefeated 1960 season with a 57–55 win over St Catherine's Angels of Racine, Wisconsin in the Knights of Columbus National Championship Tournament with Thompson scoring a team-high 15 points and adding 12 rebounds.

[7] Upon graduation, Thompson was the Friars' all-time leader in points, scoring average, and field goal percentage, and second in rebounds to former teammate Jim Hadnot.

[6] At 6 ft 10 in (2.08 m) and 270 lb (120 kg), he backed up Bill Russell, the Celtics star center, en route to consecutive NBA championships.

[12] The 1984 squad, led by 7-foot (2.1 m) center Patrick Ewing, won the Division I national championship over Houston, and Thompson became the first African-American coach to lead his team to the title.

[6] An imposing figure on the sidelines who towered over many opposing coaches and even players, Thompson was noted for a trademark white towel that he carried on his shoulder during the games,[3][6] which he did as a tribute to his mother.

[12] Thompson coached many notable players, including Ewing, Sleepy Floyd, Alonzo Mourning, Dikembe Mutombo, and Allen Iverson.

[18] In the late 1980s, Thompson got word that several of his players, including Alonzo Mourning, were associating with noted Washington, D.C. drug lord and avid Hoya fan Rayful Edmond III,[19] whose crew was connected to at least forty homicides.

Thompson, known for his volatility, quickly boiled over, and unleashed a profanity-laced tirade in which he told Edmond that he did not care about his crew's violent reputation or propensity to commit murder.

Although favored to win the international tournament, the United States was narrowly defeated by the all-professional and experienced Soviet Union in the semifinals 82–76, marking the first time the Americans did not reach the gold medal game.

The United States won its final game against Australia to capture the bronze medal, the lowest finish by an American team for men's basketball.

[6] On January 14, 1989, before the start of Georgetown's home game against Boston College, Thompson walked off the Capital Centre floor and turned coaching duties over to assistant Mike Riley.

Leo J. O'Donovan, university president, referred to as a "coach emeritus" position, assisting on academic, athletic, and community projects.

[6] After retiring from coaching, Thompson became the presidential consultant for urban affairs at Georgetown University, a basketball commentator for TNT, and host of a sports talk show, The John Thompson Show, on WTEM in Washington, D.C.[32][33] He signed a lifetime contract with Clear Channel Radio and WTEM in 2006.

He was scheduled to appear on Jim Rome's radio show in Los Angeles and wished to fly on September 11 and attend a friend's birthday party in Las Vegas on the 13th.