The school went through some financial difficulties and closed for much of the 1870s. It reopened in 1883 as "East Florida Conference High School”, then changed to “East Florida Scientific and Divinity High School”. Over the next ten years, the curriculum was expanded and the school was renamed for the third bishop of the AME Church, Edward Waters.
In 2004, Edward Waters College submitted documents to SACS to support their request for reaccreditation. A Florida Times-Union investigation in October discovered that the EWC documents plagiarized sections of text and statistics from a similar Alabama A&M University document. The Commission on Colleges voted to drop EWC from membership in SACS, thus revoking the school's accreditation, but the school appealed. A hearing was held in Atlanta during February 2005, and the appeal by Edward Waters College was denied. The school then filed a lawsuit seeking an injunction during litigation, which a federal judge granted. The judge stated that the college could show they were denied due process, and appointed two mediators. In June, the college and SACS agreed to a settlement that allowed the school to remain accredited while re-filing their accreditation documentation. The college's accreditation was reaffirmed in 2006.
Centennial Hall, which contains the Obi-Scott-Umunna Collection of African Art, is the oldest building on campus. Built in 1916, it was added to the United States National Register of Historic Places on May 4, 1976.
Edward Waters athletic teams are known as the Tigers and Lady Tigers. The college is a member of the National Association of Intercollegiate Athletics (NAIA) Division I level, primarily competing in the Gulf Coast Athletic Conference (GCAC). The Tigers formerly competed in The Sun Conference, formerly known as the Florida Sun Conference (FSC). Men's sports include baseball, basketball, cheerleading, cross country, football, golf and track & field; while women's sports include basketball, cheerleading, cross country, golf, softball, track & field and volleyball.