The parish of St. Mary is one of the oldest parishes on the island that still exists today. The parish includes the former parish of Metcalfe, which was established in 1665 by Governor Sir Thomas Modyford, and part of the former parish of St. George, which was originally settled in 1534 by Spanish settlers. In 1655, after the English captured Jamaica from the Spanish, Port Maria became known as St. Mary after the town of Puerto Santa Maria located within it. Numerous national monuments are still standing in this parish such as Rio Nuevo, which was once a thriving village during colonization but later became known as "The Lost Town" due to its destruction during an attack by buccaneers in 1730. The town holds historical significance for being the site of the last battle between invading English forces and defending Spaniards who had to flee to Cuba after their defeat.

In 1760, a slave rebellion broke out in Jamaica around Port Maria.  The leader of this rebellion was a Coromantee slave called Tacky, who belonged to the Frontier Estate.  Fort Haldane, now Grays Charity, was seized and ammunition taken by rebel forces.  The rebels then moved inland.  Many whites were killed.   After Emancipation in 1838, free villages were formed in St. Mary but the parish still basically remained one with big estates until the end of the 19th century, when only three sugar factories remained in operation.

Jamaica’s banana industry was established in the late 19th century with the decline of the sugar industry. In the late 1930s, St. Mary played a prominent role in the creation of Jamaica Producer’s Association, which was set up to prevent the continuation of the monopoly on bananas held by the United Fruit Company and other purchasing organizations. Under the umbrella of the Association, banana growers banded together to ship and market their own produce.