Anthony J. Drexel, a Philadelphia financier, founded Drexel Institute of Art, Science and Industry in 1891. The location at 32nd and Chestnut Streets was chosen because it was near lines of transportation, which would make it accessible for students from any section of the city and suburbs. In 1936, the name was changed to Drexel Institute of Technology. In February 1970, Drexel became a university.
The university currently occupies a 50-acre campus with a separate 18-acre athletic field.

The Main Building was the first building completed in 1891. Randell Hall was added in 1902 and Curtis Hall was completed in 1928. After an extensive remodeling, the latest addition to the campus, the Paul Peck Alumni Center, was opened May, 2000. Frank Furness, a famous Philadelphia architect, designed the Alumni Center. In 1997, the Sarah Drexel Van Rensselaer Residence hall, which was built in 1931, was reopened with suite-style living facilities. The W.W. Hagerty library, MacAlister and Matheson Halls and the Creese Student Center are named for former presidents of Drexel.

The Great Court in the Main Building is patterned after a 15th century museum in Vienna. The right toe of the Water Boy statue maintains its luster from the tradition of students who rub the toe for good luck in their exams. The Ryder Clock was mounted after the death of the first dean of mechanical engineering, J. Peterson Ryder, who was known for his punctuality. The statue in front of the admissions office is a copy of Nike of Samthrace, also referred to as, Winged Victory. The original statue is in the Louvre museum in Paris. There are four floors in the Main Building. The ceiling in the Great Court is not the top of the building; there is an atrium on the fourth floor that provides the natural lighting of the Great Court.

In November 1998, Drexel University assumed management of the Medical College of Pennsylvania, and Hahnemann University. With this arrangement, students have the opportunity to earn a bachelor and medical degree in seven years as well as an MD/MBA degree.