Dawson was selected by the Expos in the 11th round (pick #250) of the 1975 Major League Baseball draft. He played in 24 major league games in 1976 after making his debut on September 11. His stardom rose in 1977 when he became an everyday outfielder for the Expos, and batted .282 with 19 home runs and 21 stolen bases. He was awarded the 1977 Rookie of the Year in the National League, narrowly beating out Steve Henderson of the New York Mets. Dawson had a blend of power and speed, hitting at least 20 home runs in seven seasons with the Expos, and stealing at least 20 bases in his first seven seasons. Dawson, playing primarily center field for the Expos, also became an excellent defensive player, gaining his first of eight Gold Glove Awards in 1980. Based on his all-around excellence, Dawson was second in the National League MVP voting in 1981 (won by Mike Schmidt) and second again in 1983 (won by Dale Murphy). He was voted the Montreal Expos Player of the Year in 1981 and 1983.

Dawson played 1,443 games with the Expos, fourth highest in franchise history. As an Expo, Dawson set single-season club records for home runs (32, now seventh), RBI (113, now fourth), extra base hits (78, now seventh), and sacrifice flies (18, still first). He still holds the Expos career record for sacrifice flies (71), and is the only player to hit 200 home runs and steal 200 bases with Montreal. During his Expo days, Dawson hit two home runs in the same inning twice: at Atlanta–Fulton County Stadium against the Atlanta Braves on July 30, 1978 and at Wrigley Field against his future team, the Chicago Cubs, on September 24, 1985. As of 2019, Dawson, Willie McCovey, Jeff King, Alex Rodriguez, and Edwin Encarnacion are the only five players who had hit two home runs in one inning twice.

In 1984 Dawson appeared in The Cap, a short film about a young boy living in Montreal that was given a baseball cap by Dawson.

The major impediments to Dawson’s election to the Hall of Fame had been his ordinary career .323 on-base percentage, his statistics being diminished in stature by sluggers who played after him in the steroid era, and never playing in a World Series. Cubs teammate Ryne Sandberg campaigned for Dawson’s induction during his speech at his own Hall of Fame induction ceremony in 2005: “No player in baseball history worked harder, suffered more or did it better than Andre Dawson. He’s the best I’ve ever seen. I watched him win an MVP for a last-place team in 1987 [with the Cubs], and it was the most unbelievable thing I’ve ever seen in baseball. He did it the right way, the natural way, and he did it in the field and on the bases and in every way, and I hope he will stand up here someday.”

Dawson was the second player in the Hall of Fame whose plaque depicts him with an Expos logo, after Gary Carter. Although Dawson had played the majority of his 21-year career with Montreal, he publicly expressed his disappointment with the decision, saying it was “a little gut-wrenching” to find out he would not go in as a Chicago Cub. Dawson’s reluctance to be enshrined as an Expo stemmed, in part, from the breakdown of his relationship with the team during MLB’s collusion scandal of 1986–87, when he claims the team not only “threw him out” of Montreal, but tried to prevent other teams from signing him as a free agent. While Dawson played only six years with the Cubs, five of his eight All-Star appearances were as a Cub, and his only MVP award came in his first year with the team in 1987. The Hall noted that “Dawson had 1,575 of his 2,774 hits as an Expo, won six of his eight Gold Glove awards in Montreal and led the Expos to their only postseason series win”.

Dawson was the first player to ever win a league MVP trophy from a last place team. Dawson played five more seasons with the Cubs, and was one of the franchise’s most popular players during that time. His worst individual season came in 1989, when the Cubs won the National League East title. Then, during the NL Championship Series, Dawson slumped terribly, hitting .105 as the San Francisco Giants beat the Cubs 4 games to 1. Dawson’s .507 career slugging percentage with the Cubs is fourth highest in team history.

In October 1992 the Red Sox signed Dawson as a free agent. Dawson hit his 400th career home run with the Red Sox on April 15 at Fenway Park. Dawson sustained a knee injury early in the 1993 season in a game against the Texas Rangers which limited him to only 121 games in his first year with the Red Sox: “I got caught between sliding and standing up on a passed ball. I was on second base, and I took a chop step between strides and hit the corner of the third-base bag. I had knee surgery and [Boston] decided to use me in the DH role.”

In 1997, Dawson’s #10 was retired by the Montreal Expos in his honor (the number had been previously retired for Rusty Staub). After the franchise moved to Washington, the Montreal Canadiens raised a banner in the Bell Centre to commemorate all of the retired Expos numbers, including Dawson’s. In 2010 the Washington Nationals franchise placed Dawson in its “Ring of Honor” at Nationals Park. In 2019, Dawson was inducted into the National College Baseball Hall of Fame.

Dawson would have knee surgery the following year as well, and only managed to play 75 games in his second and final season with Boston. Dawson played his last two years with the Florida Marlins, where he played sparingly, retiring after the 1996 season. In his final game, Dawson was removed from the field as a final farewell to the fans and the game. The fans gave him a standing ovation as Dawson walked off the field. He returned to the Marlins shortly thereafter when he accepted a position in the team’s front office, where Dawson got his first World Series ring in 2003. Dawson also owns The Mahogany Grille, a soul food restaurant in Miami Gardens, Florida, and the Paradise Memorial Funeral Home in Richmond Heights, Florida.

He entered the funeral business in 2003, investing in a funeral home his younger brother owned, and became the owner and operator of Paradise Memorial in 2008. In an April 2020 Associated Press story on how he and his business were having to deal with the COVID-19 pandemic, he noted, “It’s very sad. Because people mourn and grieve differently, and they’re not getting through that process as they would under normal circumstances. You see a lot of hurt and pain.” At the time of the story, his wife of 42 years, Vanessa, was the office manager, while an uncle ran day-to-day operations.

Dawson was elected to the Baseball Hall of Fame in 2010, his ninth year of eligibility, rising from an initial vote total of 45.3% in 2002 to 77.9% in 2010. Dawson’s Hall of Fame plaque depicts him with a Montreal Expos cap.

Dawson released his autobiography If You Love This Game: An MVP’s Life in Baseball in May 2012.