McCormack graduated first in his class at Boston University School of Law. He later served two terms as state Attorney General from 1959 until 1963. His tenure was known for a strong record on civil rights.
In 1962, McCormack ran against Ted Kennedy in the Democratic primary to fill John F. Kennedy's vacated seat for the Senate. McCormack's slogan was "I back Jack, but Teddy ain't ready". During the "Teddy and Eddy" debate, McCormack attacked Ted by saying "Teddy, if your name was Edward Moore instead of Edward Moore Kennedy, your candidacy would be a farce." McCormack was largely seen as the underdog going up against the fame and fortune of the Kennedy family, and his attacks gave people the perception that he was a bully. His campaign could afford few radio and newspaper ads, nor a paid staff, and being forced to handle many of the campaign details caused him to lose seven pounds by the end of the contest. Ted Kennedy easily defeated McCormack with 65% of the vote and went on the win the general election against George C. Lodge.
McCormack subsequently lost a bid for Governor of Massachusetts in 1966.