Upon graduation from Harvard, Lupien signed a professional baseball contract with the Red Sox and played the 1939 season for the Double-A Scranton Red Sox Eastern League championship team. He made his major league debut for the Red Sox on September 12, 1940. One of his most productive seasons came in 1942 when he batted .281 with three home runs and 70 runs batted in for the Red Sox. He was traded to the Phillies where he played in 1944 and early in 1945, before serving in the U.S. Navy during World War II. In the 1944 season he hit .283 with five homers, 52 RBI, 82 runs, 23 doubles, 9 triples and 18 stolen bases. After his discharge from the Navy, Lupien played two years for the Hollywood Stars of the Pacific Coast League, where his 1947 record of batting .341, with 21 homers and 110 RBI, led to his return to the major leagues for one final season in 1948, with the White Sox.