Hershiser first gained notice as a pitcher at Bowling Green State University in Bowling Green, Ohio. He was selected by the Los Angeles Dodgers in the 17th round of the 1979 amateur draft and was assigned to their farm team in Clinton, Iowa. After four more seasons in the minor leagues with San Antonio and Albuquerque, Hershiser was called up to the Dodgers on September 1, 1983.
A fierce competitor, Hershiser was nicknamed "Bulldog" by his team manager Tommy Lasorda. He had a breakthrough season in 1985 when he led the National League in winning percentage. His best season was 1988 when he led the league in wins (23), innings (267), and complete games (15). He finished the season with a record 59 consecutive scoreless innings pitched, breaking the mark held by Dodger great Don Drysdale. In his final start of the year on September 28, Hershiser needed to pitch 10 shutout innings to set the mark—meaning not only that he would have to prevent the San Diego Padres from scoring, but that his own team would also need to fail to score in order to ensure extra innings. The Dodgers' anemic offense was obliging, however, and Hershiser pitched the first 10 innings of a scoreless tie, with the Padres eventually prevailing 2–1 in 16 innings. Hershiser almost did not pitch in the 10th inning, in deference to Drysdale, but was convinced by the Hall of Famer to take the mound and try to break the record.
He then capped the season in the World Series by pitching a shutout in Game 2 and the clinching victory in Game 5, winning the World Series MVP Award. He later received both the Cy Young Award and Sports Illustrated magazine's Sportsman of the Year award for his accomplishments in 1988.
After averaging over 250 innings per season from 1985–89, the slender Hershiser broke down from overwork in 1990 when he tore ligaments in his elbow. Hershiser returned after the injury to still be an excellent pitcher, but he never regained his level of brilliance of the late 1980s. In 1995 he joined the Cleveland Indians, and posted a 16–6 mark to play a pivotal role in helping the team reach the World Series for the first time since 1954; he also was 14–6 for the 1997 pennant-winning Indians. He later joined the San Francisco Giants (1998) and New York Mets (1999) before rejoining the Dodgers for a final season in 2000.
Hershiser appeared on the cover of Sports Illustrated three times: Twice by himself, and once in a group photo with other Dodgers.