Harding's running mate was Governor Calvin Coolidge of Massachusetts, while Cox ran with Assistant Secretary of the Navy Franklin D. Roosevelt of New York.

Harding carried Massachusetts overwhelmingly with 68.55% of the vote to Cox's 27.84%, a Republican victory margin of 40.71%.

Harding was also helped in the state by his running mate, Calvin Coolidge, a traditional Yankee Republican born in neighboring Vermont and being the popular sitting Governor of Massachusetts.

Boston had been a Democratic-leaning city prior to this, and while Calvin Coolidge would win the city once more for the GOP in 1924, Boston would defect to the Democrats for Catholic Al Smith in 1928 and become reliably Democratic in every election that followed.

He even reached eighty percent in the island county of Dukes and peninsular Barnstable.