He played in Major League Baseball (MLB) for the Arizona Diamondbacks, Baltimore Orioles, Cleveland Indians, New York Yankees, Milwaukee Brewers, St. Louis Cardinals, Washington Nationals, and two stints with the Colorado Rockies.

A right-hander both when batting and throwing, Reynolds was known for his frequent and long home runs, high strikeout totals, and defensive versatility, having been primarily a third baseman before transitioning to first base while playing for the Orioles.

In 1994 he played for the Virginia Blasters Amateur Athletic Union (AAU) baseball program, where one of his teammates was B. J. Upton.

's younger brother Justin, David Wright and Ryan Zimmerman on a Hampton Roads-based autumn showcase team called the Mets in 2000.

[2] While with the Mets, Reynolds was nicknamed "Skeletor" due to his lanky build and "Forrest Gump" because of his awkward running style.

[7] Through August 2011, he was one of 29 former UVA players to have made it to the major leagues, along with former Cavaliers Michael Schwimer, Javier López, and Zimmerman.

[12] He began 2007 with the Diamondbacks′ new Class AA affiliate, the Mobile BayBears of the Southern League, and hit .306 for them in 37 games, with six home runs and 22 RBIs.

[citation needed] On October 3, 2007, when Arizona faced the Chicago Cubs in the first game of the 2007 National League Division Series, Reynolds' seventh-inning home run off of Cubs reliever Carlos Mármol led the Diamondbacks to a 3–1 victory and a three-game sweep of the division series.

[citation needed] On September 25, Reynolds set a major league record by striking out for the 200th time in one season when he failed to check his swing against St. Louis Cardinals pitcher Joel Piñeiro.

[19] In the Diamondbacks' four-game series against the Mets on July 29 – August 3, Reynolds managed to hit the longest home run in the short history of Citi Field, at 461 feet, as well as capped off the series finale with home runs in consecutive innings (first and second).

[30] Reynolds and a player to be named later (John Hester on April 30, 2011) were traded to the Baltimore Orioles for David Hernandez and Kam Mickolio on December 6, 2010.

[31][32] From the Diamondbacks' standpoint, the transaction, which was executed by new general manager Kevin Towers, was to improve the bullpen and reduce the record-breaking strikeout total by the team's batters (1,529 in 2010).

[37] On August 7, facing Ricky Romero of the Toronto Blue Jays, Reynolds became the first player in the history of Oriole Park at Camden Yards (which was 19 years old at the time) to hit a home run into the 2nd Deck (Club Level) in Left Field.

On August 17, during a game between the Orioles and the Detroit Tigers, third baseman Manny Machado fielded a ground ball off the bat of Jhonny Peralta.

Machado threw off line to Reynolds, who had to lay all the way out to catch the ball, and was unable to keep his foot on the bag long enough to record the out.

Reynolds angrily threw his glove to the ground, causing him to be ejected by second base umpire Vic Carapazza.

Orioles manager Buck Showalter angrily argued that Reynolds could not be ejected for throwing his glove, but he too was tossed, by third base umpire Marty Foster.

Reynolds initially walked back onto the field, as if the umpires reversed the ejection call, only to return to the dugout moments later.

A tongue-in-cheek article appeared in Baseball Prospectus in January 2013 that purported to lay out evidence "proving" that Reynolds is blind.

[42] On April 13, in a game against the Chicago White Sox, he hit his second career grand slam off of Chris Sale.

[46] On August 28, Reynolds started at second base for the first time in his career while Robinson Canó and Eduardo Núñez were stricken with injuries.

[12] On December 11, 2014, Reynolds signed with the St. Louis Cardinals on a one-year, $2 million contract that included playing times incentives.

[59] On May 9, in a 10−4 victory versus the Cubs, he tied his personal best by homering in his fourth consecutive game, first achieved August 6−9, 2009.

[12][61] A free agent after the conclusion of the 2017 season, Reynolds went unsigned until April 12, 2018, when the Washington Nationals signed him to a minor-league contract.

[12] He played in 10 games for Syracuse, batting .231 with a double and a home run in 39 plate appearances,[62] before the Nationals selected his contract on May 12, after they placed starting first baseman Ryan Zimmerman on the 10-day disabled list with a right oblique strain.

[64] The next night, Reynolds went 5–5 with 2 home runs, a double, and a career-high, franchise record-tying 10 RBI in an 18–4 win over the Marlins.

It was the most RBI in a game by any player in MLB since Scooter Gennett’s 10 RBIs for the Cincinnati Reds during his 4 home run performance on June 6, 2017, and it tied the franchise record set by teammate Anthony Rendon in 2017.

On July 9, he was named the National League Player of the Week after slashing .625/.684/1.313 with 12 RBI and 3 home runs in seven games.

[67] Reynolds said he had interest from other teams but wanted to play with a contender, and expects to make spot starts or be a pinch-hitter off the bench.