The first component of the modern Wayne State University was established in 1868 as the Detroit Medical College, now the School of Medicine. In 1881, the Detroit Normal Training School was established, now the College of Education. Old Main Hall was built in 1896 as Central High School, which later began adding college classes in 1913. Those classes evolved into the Detroit Junior College in 1917, the College of the City of Detroit in 1923 and now WSU's College of Liberal Arts and Sciences. In 1919, David L. Mackenzie who served a dual role as Principal of Detroit Central High School and Detroit Junior College  was officially appointed first dean of the college that he had originated in 1917. With Mackenzie at the helm, Detroit Junior College grew to become the third-largest institution of higher learning in Michigan. The college was granted four-year degree status in 1923, becoming the College of the City of Detroit. Mackenzie continued as dean until his death in 1926. In 1920, the Merrill-Palmer Institute for Child Development was founded. It is now known as the Merrill-Palmer Skillman Institute. In 1927, the Detroit Board of Education dedicated its newest high school to the memory of Mackenzie. The three-story structure stood on the city's west side at 9275 Wyoming Avenue; Mackenzie High School closed its doors in June 2007 and was demolished in 2012.

A new pre-kingergarten-to-eighth-grade Mackenzie School opened near the high school site in 2012. In 1933, the Detroit Board of Education organized the six colleges it ran  liberal arts, medical, education, pharmacy, engineering and a graduate school  into one university. In January 1934, that institution was officially named Wayne University, taking its name from the county in which it is located. Wayne University continued to grow, adding the Law School in 1927, the School of Social Work in 1935, and the School of Business Administration in 1946. Wayne University was renamed Wayne State University in 1956 and the institution became a constitutionally established university by a popularly adopted amendment to the Michigan Constitution in 1959. The Wayne State University Board of Governors created the Institute of Gerontology in 1965 in response to a State of Michigan mandate. The primary mission in that era was to engage in research, education and service in the field of aging. Wayne State University continued growing with the additions of the College of Lifelong Learning in 1973, and the School of Fine and Performing Arts and the College of Urban, Labor and Metropolitan Affairs in 1985. Detroit College of Medicine, about 1911 The university libraries have grown to include eight libraries, the School of Library and Information Science, and the Office for University General Education.

Over the last few years, WSU has been aggressive in constructing new buildings, including the Multidisciplinary Biomedical Research Building (MBRB), a 207,000-square-foot facility that will encourage interdisciplinary work across a range of scientific areas with the goal of translating new discoveries to improve human health and society. More than 500 researchers, staff and principal investigators will work out of the building, which is scheduled to be fully operational in early 2015. On June 5, 2013, the Board of Governors unanimously elected M. Roy Wilson as Wayne State's 12th president. He was sworn in on August 1, 2013.

As a nationally recognized urban public research university, Wayne State's mission is to create knowledge and prepare a diverse body of students to excel in an increasingly complex and global society.

Anthony Bass, starting pitcher for the San Diego Padres; drafted in the 5th round of the MLB draft in 2008 Tom E. Beer, former linebacker for the Detroit Lions Joique Bell, Wayne State all time leading rusher; currently with the Detroit Lions Gregory Benko, Olympic foil fencer Ron Berger, formerly played football for the New England Patriots Rick Byas, cornerback for the Atlanta Falcons Ken Doherty, Olympic bronze medalist, decathlon (1928) Phil Emery, General Manager for the Chicago Bears Byron Krieger, a foil, sabre, and  fencer; NCAA champion; 2-time Pan Am gold medalist; 2-time Olympian; 2-time Maccabiah Games gold medalist Allan Kwartler, a sabre and foil fencer; Pan-American sabre champion and 3-time gold medal winner; 3-time Olympian, and 2-time gold medal winner at the Maccabiah Games (attended) Dan Larson, Major League Baseball pitcher (1976-1982) Stavros Paskaris, former professional ice hockey player Fred Snowden, former assistant coach at the University of Michigan; former head coach of the University of Arizona men's basketball teams; first black head coach of a major university's basketball program in America's history Allen Tolmich, Track and Field athlete, established or tied 11 U.S. track & field records in 1938 Lorenzo Wright, Track and Field athlete, Gold Medal Winner in the 1948 Olympics (400-meter relay)

Alumni Association:alumni.wayne.edu

Wayne State's campus is located in the heart of Detroit's Cultural Center Historic District, home of renowned museums, galleries and theatres. The main campus encompasses 203 acres (0.82 km2) of landscaped walkways and gathering spots linking over 100 education and research buildings. The campus is urban and features many architecturally interesting buildings. Notable examples include Helen DeRoy Hall, the Education Building, the Maccabees Building, Old Main, McGregor Memorial Conference Center, Chatsworth Tower Apartments, and the Hilberry Theatre (Wayne State University). Many of these buildings were designed by notable architects such as Albert Kahn and Minoru Yamasaki.