Founded as the Pennsylvania Female College on December 11, 1869, by Reverend William Trimble Beatty (the father of renowned operatic contralto Louise Homer), it was located in the Berry mansion on Woodland Road off Fifth Avenue in the neighborhood of Shadyside.

[7] Chatham received some national attention in 2014 when it announced that it was engaging in a period of study "considering admitting men for the first time in that college's history,"[8] resulting in "reactions of surprise and anger" from its alumnae.

The Shadyside Campus now also includes the Chatham Eastside building,[13] which serves as the home for the health science and interior architecture programs.

The university's new 388-acre (157 ha) Eden Hall Campus is located north of the city of Pittsburgh in Richland Township, Pennsylvania; it is the home of Chatham's Falk School of Sustainability & Environment.

In 2011, the university engaged the architectural team of Berkebile Nelson Immenschuh McDowell (BNIM) of Kansas City, Mo.

In 2013, the Falk Foundation made its largest and final grant to the School of Sustainability & the Environment for the completion of the Eden Hall Campus.

Chatham has both Men's and Women's varsity teams in basketball, cross country, ice hockey, lacrosse, soccer, softball, squash, swimming & diving, track & field, volleyball, and Co-ed sideline cheerleading.

[citation needed] Chatham athletics announced in November 2024 that they will be adding a Co-ed competitive cheerleading team for the 2025-2026 season.