A switch-hitter, Headley made his Major League Baseball (MLB) debut with the San Diego Padres in 2007, and also played for the New York Yankees.

Headley played college baseball for the Pacific Tigers and Tennessee Volunteers, before the Padres selected him in the 2005 MLB draft.

During the 2012 season, Headley led the National League (NL) in runs batted in (RBIs) and was honored for his hitting with a Silver Slugger Award.

He was selected to play in the 2002 Colorado Rockies Senior All-Star Game, in which he hit a home run in his first time at bat.

He also played two seasons with the Colorado Rockies Select Scout Team, and in the National Baseball Congress World Series.

[9] The San Diego Union-Tribune called Headley the Padres' best eventual prospect to fill the third base position, though it theorized it would take two years.

I'm trying to get every advantage mentally as I can – keeping track of what different pitchers have done to me in the past, or what other hitters do in certain situations against our guys, so I can position myself better – I just try to apply myself and see if I can't pick something up and use it to benefit what I'm trying to do.

Headley hit well in spring training in 2008, .371 with a team-leading 12 RBIs, but was sent to the Portland Beavers of the Class AAA Pacific Coast League to get more experience playing left field.

On June 15, 2007, after hitting .357 for the San Antonio Missions of the Double-A Texas League, Headley was brought up for 8 games because of an injury to Padres third baseman Kevin Kouzmanoff.

[citation needed] In early January 2010, the Padres traded third baseman Kevin Kouzmanoff to the Oakland Athletics, moving Headley back to third base, his original position.

On April 16, Headley hit a walk-off three-run home run off Diamondbacks pitcher Juan Gutierrez, snapping the Padres two-game losing streak.

[citation needed] During spring training in 2012, Headley set initial goals of hitting 15 home runs and recording 75 RBIs in the upcoming season after a discussion with former Padre and Hall of Fame outfielder Dave Winfield.

While the Padres were extending contracts of some of their players, they did not pursue a deal with Headley due to the potential of third base prospects Jedd Gyorko and Logan Forsythe.

He was later named NL Player of the Month for August, becoming the first Padre to be so honored since Tony Gwynn won the award in May 1997.

[12] Headley was unanimously voted the Padre Player of the Year by the San Diego chapter of the Baseball Writers' Association of America (BBWAA) after hitting .286 and leading the league in RBIs with 115.

[22] On March 17 during spring training, he fractured the tip of his left thumb when it got caught under the second base bag while he was sliding feet-first to break up a double play.

[26] On July 22, 2014, the Padres traded Headley to the New York Yankees in exchange for Yangervis Solarte and Rafael De Paula.

[27][28] Later that same day, Headley drove in the winning run for the Yankees with a walk-off single in the bottom of the 14th inning to seal a 2–1 victory over the Texas Rangers.

[29] On September 4, 2014, Headley hit a walk-off solo home run off Red Sox closer Koji Uehara to give the Yankees a come from behind 5–4 victory.

[34] With the Yankees' acquisition of third baseman Todd Frazier from the Chicago White Sox, it was announced that Headley would move to first base.