The hotel opened in January 1928 in the presence of Ohio Governor Vic Donahey, Columbus Mayor James J. Thomas, and prominent hoteliers from across the United States.
In the fall of 1939, the Van Cleve hosted Bob Chester's orchestra for a dance music program, aired nationally on CBS radio.
Through the 1960s, the Van Cleve faced a steady decline in business due to newer more modern hotels and motels being built in the area.
Instead, an anonymous donor purchased the hotel in November 1967 for between $750,000 and $1,000,000 and gave it to the Christ Episcopal Church next door.
After the restaurant and bar closed, the building remained empty until March 1969, when its furnishings were auctioned off and demolition began.