During 1998‒2012, coccidioidomycosis cases increased nationally nearly eightfold. To describe the epidemiology of coccidioidomycosis in Missouri, a state without endemic coccidioidomycosis, coccidioidomycosis surveillance data during 2004-2013 at the Missouri Department of Health and Senior Services were retrospectively reviewed. The incidence of reported coccidioidomycosis increased from 0.05 per 100,000 population in 2004 to 0.28 per 100,000 in 2013, with cases distributed throughout all regions of Missouri. Persons aged >60 years were most affected. In cases in which patients had disease manifestations, the most common were pneumonia (37%) and influenza-like illness (31%). Nearly half (48%) of patients had traveled to an area where coccidioidomycosis is endemic, whereas approximately one-quarter (26%) of patients did not report such travel. Those with history of travel to endemic areas were significantly more likely to receive a diagnosis by positive culture or polymerase chain reaction (PCR) testing, compared with those without a history of travel to endemic areas, who were more likely to receive a diagnosis by serological tests. Additional studies will be required to ascertain whether truly endemic cases exist in Missouri.