Oxcutzcab was a town dating back to Pre-Columbian times. With the fall of Mayapán in the 1440s Oxcutzcab became a regional capital ruled by the Xiu family. After the Spanish conquest of Yucatán it was re-established as a Spanish colonial town in 1550; the native temples were demolished and a large Franciscan church built.
Oxcutzcab was granted the legal status of a city in the early 19th century. In 1847 the city was sacked in the Caste War of Yucatán. In 1879 the city was linked to the capital of Mérida by railroad. In the 1990 census the population was 17,189.
In the middle of each August, the city hosts a "Festival of Oranges".