He played 15 seasons in Major League Baseball (MLB) for the Atlanta Braves, New York Yankees, and Houston Astros.

A seven-time All-Star and a six-time Silver Slugger Award winner, he won the 2017 World Series with the Astros.

He accomplished the feat in the second inning of a 7–1 victory over Roger Clemens and the Houston Astros in Game 2 of the 2005 National League Division Series.

He led all Major League catchers in homers, and his RBI total was matched only by Jorge Posada and Victor Martinez.

[7] The Braves rewarded McCann by buying out his arbitration years with a six-year, $27.8 million contract during spring training in 2007.

[8] In May 2009, Oakley, Inc. made special glasses for McCann to correct the vision problem and allow for comfort under the catcher's mask.

In the latter, he was named the MVP after driving in all three of the National League's runs with a bases-clearing double in the seventh inning (driving in Scott Rolen, Matt Holliday, and Marlon Byrd), off of Chicago White Sox reliever Matt Thornton, giving the NL a 3–1 victory, its first in the midsummer classic since 1996.

[6] During spring training, on March 9, 2011, McCann hit a line drive foul ball which struck minor league manager Luis Salazar, blinding him in the left eye.

He did this on the same day Chipper Jones tied Pete Rose's major league record for extra base hits by a switch hitter.

[17] On July 14, 2013, McCann was chosen by National League manager Bruce Bochy to replace injured Braves first baseman Freddie Freeman in the 2013 All-Star Game.

On November 23, 2013, McCann agreed to a five-year, $85 million contract with the New York Yankees, with a vesting option for a sixth year.

On May 28, 2014, with limited options at first base, manager Joe Girardi slotted McCann into his first career start at first against the St. Louis Cardinals, going 2-for-4 with an RBI, a run scored, and a walk in a 7–4 Yankee win.

On September 6, 2015, McCann hit his career-high 25th home run of the season, a game-tying three-run shot off of Chris Archer of the Tampa Bay Rays.

After the Yankees released Alex Rodriguez, rookie catcher Gary Sánchez was brought up to share in catching duties.

[26] On November 26, 2018, McCann signed a one-year, $2 million contract with the Atlanta Braves, marking his return to the club.

[32] On October 9, 2019, shortly after the Braves' Game 5 loss in the National League Division Series against the St. Louis Cardinals, McCann announced his retirement from baseball.