Youngstown State University traces its beginnings to a commercial law course offered by the Young Men's Christian Association (YMCA) in 1908. The YMCA had offered high school level and vocational courses since 1888, but it wanted to meet the college-level needs of area residents in a society undergoing rapid industrialization and urbanization. The "Y" offered courses on law, business, and engineering, and in 1910, it even instituted a School of Law that granted no degree but prepared students to take the bar exam. In 1916, the YMCA incorporated all of its educational work under the Youngstown Association School.
 
By the early 1920s, the Ohio Board of Education granted the School of Law the power to confer the Bachelor of Science in Law degree, and in 1924 the School of Commerce and Finance the right to confer the bachelor's degree in commercial science. The YMCA also offered courses to prepare teachers for certification, a program that evolved by 1927 into a separate school named Youngstown College and recognized by the State Department of Education.  That same year, the school also established the College of Liberal Arts. Throughout the 1920s, the schools of law and commercial science were called the Youngstown Institute of Technology, which began a move from downtown to the present location with the purchase of several mansions owned by the Wicks and other prominent Youngstown families.

In 1931, the YMCA constructed its first classroom building, the present-day Jones Hall, and appointed Howard Jones as the educational director. By the mid-1930s, the Board of Directors decided to incorporate with the official name of Youngstown College separate from the other "Y" educational efforts; they appointed Howard Jones as the first president, a position he held until 1966.

In 1944, the trustees of the Young Men's Christian Association transferred control of the institution to the members of the Corporation of Youngstown College, and in 1955 the corporation was rechartered as The Youngstown University. The University joined the Ohio system of higher education in September 1967 as Youngstown State University.

Dana's Musical Institute, founded in nearby Warren in 1869, became Dana's Musical Institute of Youngstown College in 1941. In 1946, the Engineering Department, organized several years before, became the William Rayen School of Engineering; two years later, the Business Administration Department became the School of Business Administration; and in 1981 the school name was changed to the Warren P. Williamson, Jr. School of Business Administration. In 1960, the Education Department became the School of Education.

The Graduate School and College of Applied Science and Technology were created in 1968, and, in 1974, the College of Creative Arts and Communication was established.

In 1972, Youngstown State University, with the University of Akron and Kent State University formed a consortium to sponsor the Northeastern Universities College of Medicine, which enrolled its first students in 1975.

In 1991 the engineering technology departments separated from CAST and joined the new College of Engineering and Technology; the remaining departments formed the new College of Health and Human Services.

In  2007, the Rayen College of Engineering and Technology incorporated the science and mathematics departments from the College of Arts and Sciences. This reorganization linked science, technology, engineering, and mathematics in one academic college, and the humanities and social sciences in another college.

Youngstown State University now consists of the College of Graduate Studies and six undergraduate academic colleges:

  • Beeghly College of Education
  • Bitonte College of Health and Human Services
  • College of Creative Arts and Communication
  • College of Liberal Arts and Social Sciences
  • College of Science, Technology, Engineering, and Mathematics
  • Willamson College of Business Administration

Degrees offered range from the associate, bachelor’s, and master’s to a Doctorate in Educational Leadership, a Doctor of Physical Therapy, and a Doctor of Philosophy in Materials Science and Engineering.