Doerr was purchased by the Boston Red Sox for $75,000 in November 1935 and joined the San Diego Padres of the Pacific Coast League for 1936. He batted .342 with the Padres and made his major league debut with the Red Sox just 13 days after his 19th birthday.

In his 1937 rookie major league season, Doerr played 55 games and batted .224. He became Boston's regular second baseman in 1938 and was an all-star selection by 1941. He had one of his best seasons in 1944 when he was named the American League's Most Valuable Player. Playing 125 games he batted .325, hit 15 home runs and drove in 81, while leading the league with a .528 slugging percentage.

Doerr's major league career was put on hold on September 20, 1944 when he entered military service with the Army. A punctured eardrum, suffered when he was six years old, might have kept him out of service but he passed his physical examination and reported to Camp Roberts, California where he served for the duration.

Sergeant Doerr regularly played baseball at Camp Roberts, a replacement training center with a population that peaked at 45,000 in 1945. He received his discharge from service on December 15, 1945.

Doerr returned to the Red Sox in 1946 and despite a drop in average to .271, he drove in 116 runs and continued to play outstanding defense at second base.

He remained the regular second baseman of the Red Sox until he was forced to retire after the 1951 season due to serious back problems.

Doerr scouted for the Red Sox from 1957 to 1966, then spent three seasons -1967 to 1969 - as a Red Sox coach. In 1977, he became the first hitting coach of the expansion Toronto Blue Jays.

Bobby Doerr was voted into the Baseball Hall of Fame by the Veterans Committee in 1986.