She nursed many soldiers through cholera and yellow fever

In 1850, cholera struck Jamaica and killed approximately 32,000 people there. Before going to visit her brother in Cruces, Panama, in 1851, Mary cared for patients during the epidemic.

The following year, a severe cholera outbreak hit Panama. Having helped a patient survive, Seacole's reputation has grown. The only other option was an inexperienced doctor, so many patients went to see her. The treatment for Seacole was only marginally effective. She taxed the wealthy but provided free care for the needy.

Her reputation as a healer and nurse spread across the village when she successfully treated the first sufferer. She sought to rehydrate patients using water that had been cooked with cinnamon rather than merely treating them with opium. She also employed poultices and calomel. As the outbreak came to an end, she herself became ill but lived.

After a yellow fever outbreak in Kingston in 1853, Mary went back there because her nursing talents were needed. The British Army asked her to oversee the medical staff at the Up-Park headquarters in Kingston.