Upon the death of Indiana University's first president Andrew Wylie in 1851, the Board of Trustees sought Lathrop as his replacement. Elsewhere occupied, he declined. Upon the abrupt departure of President William Mitchel Daily in 1859, the Indiana University Board of Trustees once again sought to fill the office with Lathrop. This time, he accepted, and took office on September 20, 1859. His inauguration took place July 11, 1860 and directly thereafter he submitted his resignation to the Board.
