The son of a Baptist minister, Francis Wayland graduated from Union College in 1813 and for the next two years continued his medical studies in his native New York City. In 1816 he abandoned medicine to study for the ministry, but lack of funds forced him to withdraw from the Andover Seminary. In 1817 he returned to Union College and remained there as a tutor until 1821, when he became a minister at the First Baptist Church in Boston. Wayland's sermons gained him notoriety in the Baptist community, which in turn led to his receipt of an honorary degree from Brown in 1822 and his election to the Corporation in 1825. Wayland returned to Union in 1826 as professor of mathematics and natural philosophy, though his third stay there proved to be the shortest. That December, he was elected Brown's president, and took office two months later. A beloved, though stern, figure on campus, Wayland sought to squelch the unruliness that beset the student body prior to Messer's resignation. He ordered that officers of the College visit students' rooms and "occupy rooms in the College, during the hours appropriated for study." Students alleged he "had a heavy foot for a student's door when it was not promptly opened after his official knock."
Wayland wrote several widely recognized textbooks on the topics of moral and intellectual philosophy and political economy. He was also an advocate of changes in higher education. In his own classes, he encouraged student analysis of the lesson and free discussion, both of which were innovative for the time. Lack of support for his progressive views led to his offer of resignation in 1849. Discussions with the Corporation resulted in the withdrawal of his resignation.
His 1850 Report to the Corporation of Brown University on changes in the system of collegiate education outlined Brown's first "new curriculum." Wayland posited in the report that "every student might study what he chose, all that he chose, and nothing but what he chose." This led to more flexible entrance and degree requirements, which were later criticized, and to the introduction of electives. After effecting remarkable change in the institution during his tenure, Wayland retired in 1855, and lived only blocks from campus until his death in 1865.