He played in Major League Baseball (MLB) for the Giants, Colorado Rockies, Los Angeles Dodgers, Atlanta Braves, and Texas Rangers.

He made his MLB debut that day[13] and collected his first major league base hit against Arizona Diamondbacks starter Joe Saunders.

[15][16] He spent the rest of the 2012 season with the Colorado Springs Sky Sox, the Rockies' AAA affiliate, and continued to play for them in 2013.

[17] When Carlos González went on the disabled list, Culberson and Corey Dickerson entered a platoon situation in left field.

On May 4, 2014, Culberson hit a pinch-hit walk-off two-run home run off New York Mets closer Kyle Farnsworth, giving the Rockies an 11–10 victory.

Nearer to opening day, he was diagnosed with a herniated disc in his back, and played in only five games at the major league level.

[20][21] After the season, he was granted free agency by the Rockies and signed a minor league contract with the Los Angeles Dodgers.

[30] He remained in the minors for the conclusion of the AAA season, hitting .250 in 108 games[28] and returned to the majors with the Dodgers on September 4.

[33] On December 16, 2017, the Dodgers traded Culberson, Adrián González, Scott Kazmir, Brandon McCarthy, and cash considerations to the Atlanta Braves for Matt Kemp.

[37] Culberson pitched professionally for the first time on August 17, taking the mound in the ninth inning of a game against the Colorado Rockies.

[42][43] On September 14, Culberson was struck by a pitched ball thrown by Fernando Rodney of the Washington Nationals, and left the game.

[48] On September 30, 2020, Culberson was selected back to the 40-man roster to be active for the Wild Card Series matchup against the Cincinnati Reds.

[53] On December 28, 2020, Culberson signed a minor league deal with the Texas Rangers and was invited to spring training.

[62] On March 31, 2023, Culberson signed a minor league contract to return to the Atlanta Braves organization and was assigned to the Triple-A Gwinnett Stripers.

[71] His only appearance came as a pinch hitter in the team's July 16 game against the Chicago White Sox, and he collected a single off of Jesse Scholtens in his only at–bat.

[77] He made his first spring training appearance as a pitcher on February 29, pitching one inning and giving up a single and no runs.