He was a member of five World Series championship teams: 1992 with the Toronto Blue Jays and 1996, 1998, 1999 and 2000 with the New York Yankees.

Prior to the 1987 season, Cone was traded with Chris Jelic to the New York Mets for Ed Hearn, Rick Anderson and Mauro Gozzo.

His first start was a complete game shutout over the Atlanta Braves,[9] and he went on to post a 9–2 record with a 2.52 ERA in the first half of the season to earn his first All-Star nod.

For the season, Cone went 20–3 with a 2.22 ERA to finish third in National League Cy Young Award balloting.

Cone became a newspaper commentator on the playoffs for the New York Daily News, and incited controversy after the Mets' 3–2 victory in game one by saying Dodgers game one starter Orel Hershiser "was lucky for eight innings", and ripping closer Jay Howell:[10] We saw Howell throwing curveball after curveball and we were thinking: This is the Dodgers' idea of a stopper?

In a well-known incident on April 30, 1990, against the Atlanta Braves, Cone covered first base on a throw from second baseman Gregg Jefferies, which should have retired batter Mark Lemke.

Arguing with Williams, and thinking time had been called, Cone held the ball while two Braves runners (Dale Murphy and Ernie Whitt) scored.

[15][16] Cone spent over five seasons in his first stint with the New York Mets, most of the time serving as the team's co-ace alongside Dwight Gooden while leading the National League in strikeouts in 1990 and 1991.

Cone headed to the postseason for the second time in his career as the Blue Jays won the American League East.

[citation needed] Cone returned to his hometown Kansas City Royals as a free agent for the 1993 season.

He improved to go 16–5 with a 2.94 ERA (171 ERA+) in the strike-shortened 1994 season to win the American League Cy Young Award, and finish ninth in MVP voting.

Four days after the strike ended, the Royals traded Cone back to the Blue Jays, in exchange for Chris Stynes, David Sinnes and Tony Medrano.

Cone was 9–6 with a 3.38 ERA for Toronto, however, the Jays were 35–47 and in fifth place when they struck a deal with the second-place New York Yankees.

On July 28, 1995, the Blue Jays sent Cone to the Yankees for Marty Janzen, Jason Jarvis and Mike Gordon.

[21] When the Yankees acquired Cone, they were on a six-game winning streak, though still trailing the Boston Red Sox for the division lead.

[39][40][41] After the game, Cone was met at his clubhouse locker by Larsen and Berra, who together wrapped him in a bear hug.

[46] In 2001 Cone pitched for the rival Boston Red Sox, performing with mixed but mostly positive results, including a 9–7 win–loss record and a 4.31 ERA.

However, his comeback attempt with the crosstown rival Mets in 2003 annoyed Yankees owner George Steinbrenner and Cone was told he would not be welcomed back.

[53] On April 19, 2011, Cone returned to the Yankees broadcast booth in Toronto, working as analyst for a Yankees-Blue Jays series along with Ken Singleton.

After the 2021 season, Cone began co-hosting the podcast "Toeing the Slab" with Justin Shackil for Jomboy Media.

[55] In 2022, Cone was announced to be part of the Sunday Night Baseball broadcast team on ESPN along with Karl Ravech, Eduardo Pérez, and Buster Olney.

[56] On July 17, 2009, Cone testified as a witness (representing the Democratic Party) before the Senate Judiciary Committee during the Supreme Court nomination hearings for Judge Sonia Sotomayor.

The three women later amended their lawsuit against Cone, accusing him of having lured them into the bullpen area at Shea Stadium in 1989 and masturbating in their presence.

One of the women settled her claims out of court based upon Cone calling her a "groupie"; all sexual accusations were dismissed.