He played in Major League Baseball (MLB) for the Boston Red Sox, Pittsburgh Pirates, Philadelphia Phillies, Oakland Athletics, Cleveland Indians, St. Louis Cardinals, and Kansas City Royals.

Moss climbed up the ladder of minor league ball, starting with the Gulf Coast Red Sox.

He was optioned back to Triple-A Pawtucket on August 10 to make room for Hinske, who was returning from bereavement leave.

[3] During the MLB Japan Opening Series 2008 at the Tokyo Dome, Moss hit his first major league home run.

[8] On July 31, Moss was traded along with pitcher Craig Hansen to the Pittsburgh Pirates in a three-team deal that sent Manny Ramirez to the Los Angeles Dodgers and Jason Bay to Boston.

[10] After hitting 3-for-37 in spring training in 2010, and batting .154 in 26 at-bats during the beginning of the season,[10] Moss was designated for assignment by the Pirates on March 29.

[13] Playing in Class AAA, Moss considered retiring from baseball so that he could return to Georgia and work as a firefighter.

[14] Moss earned his third career walk-off by hitting a single, allowing Yoenis Céspedes to score, against the New York Yankees on July 20.

[15] Moss again earned another walk-off, this time with a home run, in the bottom of the 10th inning on September 29 against the Seattle Mariners.

[10] Moss had a hot start to the 2014 season with a .265 batting average, 23 home runs, and 71 RBI (only behind A's teammate third baseman Josh Donaldson).

Moss's 5 RBI night set a new record for the Athletics for most RBIs in a single postseason game, but it was not enough to secure victory for the A's as the Royals won 9-8.

[21] On July 30, 2015, the Indians traded Moss to the St. Louis Cardinals in exchange for minor league pitcher Rob Kaminsky.

[22] His first RBI for the club occurred the next day, also against the Rockies, a game-winning single to score Jason Heyward in the bottom of the ninth inning.

On September 1, Moss hit a three-run, walk-off home run against the Washington Nationals at Busch Stadium for an 8–5 win.

[31] On January 29, 2018, Moss, along with Ryan Buchter, was traded to the Athletics in exchange for Jesse Hahn and Heath Fillmyer.