After playing the 1985 season for the Kentucky Wildcats, Leyritz went undrafted by Major League Baseball (MLB), but was signed as a free agent by the New York Yankees.

His playing days were highlighted by a pair of memorable postseason home runs he hit with the Yankees in 1995 and 1996 in comeback wins.

In Game 2 of the 1995 American League Division Series against the Seattle Mariners at Yankee Stadium, in rainy conditions, Leyritz hit a walk-off two-run home run to right-center field in the 15th inning, giving the Yankees a 7–5 victory and a two-games-to-none lead in the best-of-five series.

The home run was surrendered by Mariners pitcher Tim Belcher, who was famously involved in a profanity-laced incident with a cameraman covering him walking through the tunnel to the clubhouse afterwards.

The best known of Leyritz's playoff heroics occurred in Game 4 of the 1996 World Series against the Atlanta Braves at Atlanta–Fulton County Stadium.

Facing Atlanta closer Mark Wohlers with one out and two runners on base, Leyritz hit a three-run home run to left field to tie the game and cap the improbable Yankee comeback.

[3] After the 1996 season, the Yankees traded Leyritz to the Anaheim Angels for two players to be named later (PTBNL): minor leaguers Jeremy Blevins and Ryan Kane.

On July 29, 1997, the Angels traded Leyritz and a PTBNL (minor leaguer Rob Sasser) to the Texas Rangers for Ken Hill.

[4] After the season, the Rangers traded Leyritz to the Boston Red Sox with Damon Buford for Mark Brandenburg, Bill Haselman, and Aaron Sele.

[5] On June 20, 1998, the Red Sox traded Leyritz with Ethan Faggett to the San Diego Padres for Carlos Reyes, Mandy Romero and Darío Veras.

The most dramatic of them came in Game 2 of the National League Division Series against Houston Astros pitcher Billy Wagner.

In Game 3, Leyritz hit the eventual game-winning home run against Scott Elarton in the bottom of the 7th inning that broke a 1–1 tie.

During player introductions in Game 1 at Yankee Stadium, Leyritz received a standing ovation from the fans who remembered his heroics from two years earlier.

NBC commentator Bob Costas remarked incredulously about Leyritz after the home run, "You could send this guy to a resort in the spring and summer, as long as he comes back in October.

On June 8, 2006, while doing an interview on the Opie and Anthony show on XM Satellite Radio, Leyritz admitted to using amphetamines during his playing career when they were not against the rules.

After each pitch that Leyritz did not put into play or strike out on, he grabbed the bat by its center and twirled it at his hip like a baton.

[citation needed] In October 2007, Leyritz worked with Harold Reynolds and Chris Myers covering the pre- and post-game reports on the field for the 2007 Playoffs and World Series for Fox.com.

[16] During his playing days, Leyritz and his wife brought foster children to see games at Yankee Stadium and contributed to Covenant House and Police Benevolent Association.