In 1852 the regents hired Henry Philip Tappan as the university’s first president. His vision of a great university on the German model laid the foundation for what has become one of the premier universities of the world. During his tenure, the Medical and Law Departments were added to the original Literary Department and the dormitories converted to classrooms. A firm believer in scientific research and the practical application of knowledge, Tappan broke with the past by recruiting faculty based on intellectual accomplishments rather than religious denomination.

Henry Tappan's liberal approach and confident manner offended the regents, who forced his resignation in 1863, despite vigorous public protest. Later President James B. Angell said Tappan was "the largest figure of a man that ever appeared on the Michigan campus. And he was stung to death by gnats!"