In the 1850s and 1860s, CTS founder Stephen Peet was a leader in a new generation of 19th-century American abolitionists no longer content to wait for the end of slavery nor to tolerate those who defended it.

Because of a conviction that training for ministry needed to combine the study of Christian faith and the world of secular knowledge and action, during President Ozora Davis' tenure in 1900s, CTS moved to the vicinity of the University of Chicago.

[8] In the 1920s, Anton Boisen, a pioneer in the hospital chaplaincy movement and founder of the Council for the Clinical Training of Theological Students, began lecturing every fall quarter in the social ethics department of CTS.

His work to help theological students better understand and minister to physically, mentally, and emotionally ill people ultimately led to the founding of the Association for Clinical Pastoral Education.

[9] Jackson dropped out of the Master of Divinity program just three courses short of degree completion in order to work on the civil rights movement full time.

He went on to found Operation PUSH (People United to Serve Humanity), a Chicago counterpart to the southern civil rights movement that focused on the economic empowerment of African-Americans and poor people of all races, and the Rainbow Coalition, which worked to unite disenfranchised American groups, from racial minorities to small farmers, in order to exercise political power.

In 1986, the seminary awarded Archbishop Desmond Tutu an honorary Doctor of Divinity degree for his activism to liberate black South Africans.

[13][14] CTS is also home to the Lesbian Gay Bisexual and Transgender Religious Archives Network, and the seminary's Heyward Boswell Society for LGBTQ people and allies engages students across campus in social activities.

CSBFL sponsors the annual C. Shelby Rooks lecture, which brings outstanding black theologians, ministers, activists, and non-profit leaders to campus.

[15] In 2009, CTS became the first free-standing Protestant seminary to endow a faculty chair in Jewish studies, with the hope of advancing interfaith engagement and multi-faith education.

[12] The next year, CTS founded the Center for Jewish, Christian, and Islamic Studies (JCIS), the first American program of its kind based in a free-standing theological seminary.

[12][16] In 2019, CTS began a partnership with Bayan Claremont to provide both a graduate certificate and an accredited Master of Divinity in Islamic Chaplaincy at the seminary's Hyde Park campus.

The original CTS building complex included stained glass windows, medieval style groin vaulting, furniture, lighting fixtures, ceramic ornament and tile work, and architectural relics—all of the highest quality of the day.

The Commons is also home to a number of rare books, including a 1670 first quarto edition of Thomas Hobbes’ Leviathan published in London by Johannem Tomsoni.