The Baltimore Orioles selected Baylor in the second round of the 1967 MLB draft. He received a $7,500 signing bonus from the Orioles. In 1970, he led the league with 34 doubles, 15 triples, 127 runs, and 140 games-played while playing for Rochester. The following year, he again led the league in doubles with 31 for Rochester. Baylor played for the Orioles from 1970 to 1975. In a transaction influenced by imminent free agency after the season, he was traded with Mike Torrez and Paul Mitchell to the Oakland Athletics for Reggie Jackson, Ken Holtzman and minor-league right-handed pitcher Bill Van Bommel on April 2, 1976.

In 1977, Baylor signed with the California Angels as a free agent. He led the American League (AL) with 139 runs batted in (RBIs) and 120 runs in 1979, and he was an AL All-Star. He won the AL’s MVP award and led the Angels to their first-ever AL Western Division title. Baylor signed with the New York Yankees in 1983. He was traded to the Boston Red Sox for Mike Easler in 1986.

While a member of the Red Sox, Baylor delivered a key hit in the 1986 American League Championship Series when he hit a two-run home run with one out in the top of the ninth inning during game five against the California Angels. At the time, the Angels led the series three games to one and were one out away from their first ALCS victory. The Red Sox went on to win the game and eventually the ALCS, denying the Angels their first trip to the World Series. Al Michaels, broadcasting the game for ABC, called it the greatest baseball game he had ever seen.

Baylor reached the World Series three times in his career, in consecutive years with three different teams. Baylor played in the World Series with the Red Sox in 1986, the Twins in 1987, and the A’s in 1988, and he was on the winning side in 1987. Baylor is one of two players in history to accomplish this feat; Eric Hinske is the other. Baylor was a power hitter known for crowding the plate. He set the Red Sox team record for most hit by pitches in a season (35 in 1986); in his career, he was hit by pitches 267 times, fourth-most all time. Baylor retired with 285 stolen bases, 2,135 hits, and 338 home runs.

In 1987, he was traded to the Minnesota Twins for a player to be named later (Enrique Rios). He signed with the Athletics for 1988, his final season as a player.

After retiring as a player, Baylor served as a hitting coach for the Milwaukee Brewers and St. Louis Cardinals until he was named the manager of the expansion Colorado Rockies. He led the team for six years from 1993 to 1998. The Rockies posted their first winning record (77–67) in 1995 and made the postseason as the wildcard team. As a result, Baylor won the National League Manager of the Year Award.

After the 1998 season, Baylor was fired. He finished his Rockies managerial career with a regular season record of 440–469 and a post–season record of 1–3. He became the hitting coach for the Atlanta Braves in 1999 and was hired to manage the Chicago Cubs in 2000, a job he held through the 2002 season. He had a record of 187–220 with the Cubs. From 2003 to 2004, he served as the bench coach for the New York Mets. He spent the 2005 season with the Seattle Mariners as hitting coach under manager Mike Hargrove and was as a fill-in analyst for MASN in 2007 for Washington Nationals broadcasts.

Baylor was diagnosed with multiple myeloma in 2003. He died on August 7, 2017, at the age of 68.

Baylor agreed on a two-year contract to become hitting coach for the Arizona Diamondbacks for the 2011 and 2012 seasons. He was hired by the Los Angeles Angels of Anaheim as their hitting coach for the 2014 season. On March 31, 2014, Baylor suffered a fracture to his right femur while catching the ceremonial first pitch of the 2014 season, thrown by Vladimir Guerrero. On April 1, 2014, he had surgery to have a plate and screws inserted into his leg. On October 13, 2015, the Angels announced that Baylor would not return as the team hitting coach in 2016.