In keeping with Baptist ideas about equality, the school came to accept women as well as men, and students of all races.

This institution is both the first college in Illinois and one of the first between the Alleghenies and the Mississippi River[2] In 1910 Andrew Carnegie, the prominent industrialist and philanthropist, donated $15,000 ($490,500 in 2023) for construction of a library.

In a letter that appeared in the correspondence section of the American Chemical Society's Journal of Chemical Education, Sigma Zeta was offered as an alternative for small colleges to the existing Sigma Xi honor society.

In 1950 Shurtleff reached its peak enrollment of 700 students, also seeing its highest number of graduates that year, 99.

The school ceased operating as Shurtleff College on June 30, 1957, when it became part of the Southern Illinois University system.