From 1983 through 1994, he played in Major League Baseball (MLB) for the Los Angeles Dodgers (1983–85), Pittsburgh Pirates (1985–90), Atlanta Braves (1991–93), and Houston Astros (1994).

Though thrice ranking among the minor league home run leaders, he batted no higher than .184 in limited playing time before getting traded to the Pirates in 1985.

After a knee injury cost him most of the 1989 season, he hit 15 home runs in 1990 as the Pirates reached the playoffs, losing to the Cincinnati Reds in the NLCS.

He was getting the majority of the playing time at first base in 1993 until the Braves acquired Fred McGriff in July, relegating Bream to a reserve role for the rest of the year.

Bream hoped to be drafted by a Major League Baseball (MLB) team out of high school, but when none selected him, he decided to attend college instead.

Bream made it all the way to Triple-A before the end of the year, hitting a home run in three games with the Albuquerque Dukes of the Pacific Coast League (PCL).

His home run total (three) was identical to what it had been with the Dodgers earlier in the year, but Bream batted .284 with 15 RBI in the 26 games he played with Pittsburgh.

[20] In late June and July, he was part of a platoon system at first base with Mike Diaz, a right-handed hitter who got starts against left-handed pitchers.

[22] In the first game of a doubleheader on August 16, he had four hits and four RBI, including a home run against Kevin Gross, in a 6–1 victory over the Philadelphia Phillies.

[23] On August 22, he had a season-high five hits and five RBI, including a two-run home run against Cliff Speck, in a 16–5 victory over the Atlanta Braves.

[26] On April 20, 1987, Bream had four hits and three RBI, including home runs against Rick Aguilera and Randy Myers, in a 9–6 victory over the New York Mets.

[31] Bream was again platooned at first base in 1988, this time with Randy Milligan, who got the Opening Day start because left-hander Shane Rawley was pitching for the Phillies.

[1] Bream tied his career high with 37 doubles, fourth in the NL behind Andrés Galarraga's 42, Rafael Palmeiro's 41, and Chris Sabo's 40.

[47] On July 31, Bream had three RBI, including a two-run home run against Shawn Boskie, in a 9–1 victory over the Cubs that moved Pittsburgh into a tie with Chicago for the NL East lead.

[2] It had taken three knee operations to get Bream back in playing shape after his injuries in 1989; for his perseverance, he was named the winner of MLB's Hutch Award after the season.

"[2] Bob Collier of the Pittsburgh Post-Gazette wrote in 2006 that Sean Casey was "the first real first baseman to walk into [the Pirates' clubhouse] in about 16 years, or since the fate-torturing departure of Sid Bream.

In Game 3 of the NLCS against the Pirates, Bream entered as part of a double switch in the eighth inning and hit a three-run home run against Rosario Rodríguez in a crucial 10–3 victory.

[2][62] Bream only played four (and only started two) of the seven NLCS games, batting .300 as the Braves defeated the Pirates, becoming the first NL team to win the pennant after finishing in last place the year before.

[65] Assessing the likelihood of a Twins-Braves World Series rematch, Jim Donaghy of the Associated Press wrote in midseason that part of the key for the Braves was "a better second half from David Justice and Sid Bream.

[2] The Pirates carried a 2–0 lead into the bottom of the ninth inning under the pitching of their ace, Doug Drabek, needing just three outs to make the World Series.

However, Drabek gave up a leadoff double to Terry Pendleton, then allowed another runner, David Justice, on an infield error by second baseman José Lind.

Reliever Stan Belinda replaced him on the mound, and managed to get two outs, despite giving up a run on a sacrifice fly by Ron Gant.

Then, Braves third-string catcher Francisco Cabrera belted a single to left field, and Justice scored easily to tie the game.

Pirates left fielder and eventual NL Most Valuable Player Barry Bonds fielded the ball as Bream, one of the slowest runners in baseball, went as fast as he could towards home plate.

On a pitch in which he checked his swing, Bream hit a grand slam through the thin air at Mile High Stadium, tying a game the Braves had trailed 6–0 but won 8–7.

[77] On July 19, the Braves acquired first baseman and defending NL home run leader Fred McGriff from the Padres, and Bream was relegated to pinch-hitting for the rest of the season.

[82] This time, he made just one appearance in the NLCS against the Phillies, entering as part of a double switch in Game 2, singling against Larry Andersen in the ninth, and scoring a run in Atlanta's 14–3 victory.

[86] His last appearance of the year came on July 27, when he pinch-hit for John Hudek in the 10th inning of a game against the Reds and singled against Jeff Brantley in Houston's 12-inning, 7–1 victory.

[75][90] A son, Tyler, attended Liberty University and was drafted by the Arizona Diamondbacks in the 42nd round (1264th overall) in 2011, playing for two seasons in their minor league system.

[92] Bream was hired in 2008 to be the hitting coach for the State College Spikes, a Pirates' affiliate in the New York-Penn League, but he only served one year in that capacity.