He played in Major League Baseball (MLB) for the Baltimore Orioles, Washington Nationals, and St. Louis Cardinals.

[4][5] Wieters finished his junior season ranked tied for sixth in the Yellow Jacket record books with 54 career doubles with 198 runs batted in along with 16 saves in his three years on the Flats.

[citation needed] Wieters hit .343 in 35 spring training at bats for the Orioles in 2009, but was sent down to Triple-A Norfolk to start the season.

[citation needed] Although Wieters disappointed some observers because of his difficulties handling the Baltimore pitching staff, he established himself as a solid defensive catcher in 2010, throwing out many runners, while also hitting for power and a fairly good average at the plate.

[citation needed] Wieters earned a Fielding Bible Award and a Gold Glove in 2011 as the best defensive catcher in MLB, and American League, respectively.

[13][14] On April 16, 2012, Wieters helped the Orioles rally to beat the Chicago White Sox in 10 innings by hitting his first career grand slam.

On May 29, Wieters was ejected for the first time in his career for arguing that two pitches thrown by Miguel Gonzalez were strikes, not balls, as ruled by home plate umpire Doug Eddings.

On Opening Day, April 2, 2013, Wieters became the first Oriole to ever hit a home run against Tampa Bay Rays starter David Price, a two-run shot in the top of the first.

[16] While Wieters did finish 2013 with a career-low batting average of .235, he also hit 22 home runs and a career-high 29 doubles, as well as leading all MLB hitters with 12 sacrifice flies.

He was still on the disabled list on June 11, when he was the leading American League catcher in the vote to determine the All Star Game starters.

[17] On June 16, the Orioles announced that Wieters would undergo Tommy John elbow reconstruction surgery the next day, ending his 2014 campaign.

Wieters began the 2015 season on the 15-day disabled list in an effort to continue recovering from last year's Tommy John surgery.

On July 27, Wieters hit his fourth career walk-off home run, helping the Orioles's beat the Atlanta Braves by a score of 2–1.

Wieters had a chance to become a free agent at the end of the 2015 season, but on November 13 he accepted the Orioles' $15.8 million qualifying offer and remained with the club.

Wieters made the All-star team as the backup catcher for the AL squad,[21] after posting a .258/.310/.418 slash with nine home runs and 37 RBIs.

On August 14, Wieters collected a career-high five hits after going 5-for-5, scoring two runs, and having a double and triple in an 8–7 Orioles comeback victory over the San Francisco Giants.

On August 30, Wieters hit a game-winning two-run homer against the Toronto Blue Jays in the eighth inning, securing a 5–3 victory for the Orioles.

[22] Wieters continued wearing #32 after relief pitcher Koda Glover agreed to change his number to #30 to accommodate his new teammate.