Duquesne was founded on Oct. 1, 1878, as Pittsburgh Catholic College by the Rev. Joseph Strub and the Congregation of the Holy Ghost. The College's 40 students and six faculty members held classes in rented space above a bakery on Wylie Avenue, in Pittsburgh's Hill District.

Duquesne's original "Old Main" building was constructed in 1885, as a result of the University's growth. This five-story red brick landmark was, for years, the highest point on the Pittsburgh skyline. It is still actively used as the administrative building on campus.

On May 27, 1911, the name was changed to Duquesne University of the Holy Ghost. The university's first professional school, the School of Law, was also established this year.