Henry Ware, Sr., loved to play more than to farm—or to go to school—in Sherborn, Massachusetts, where he was born. However, his classes were limited to six to ten weeks in the winter.

Henry's father died when he was fifteen, so his elder brothers generously pooled their small resources to enable him to attend and to graduate from Harvard College in 1785, the first scholar of his class.

After preparing for the ministry with Rev. Timothy Hilliard of the First Parish in Cambridge, he was called to Hingham's First Church ("Old Ship") in 1787, serving until 1805, when he was elected to the Hollis Professorship of Divinity in Harvard College. Some of the Overseers opposed his election because he was understood to be a Unitarian. When Dr. Jedediah Morse published his opposition, the decision was affirmed by thirty-three to twenty-three.

Professor Ware, despite that early battle with the Calvinists, was so highly esteemed that he twice served as acting president of Harvard.