The Eastern Orthodox Church traces its origins in North America to two key moments. The first was in 1768, with a short-lived colony of a few hundred Greeks in New Smyrna, Florida, which was in British hands at the time. This community disbanded because of the mismanagement of the plantation owner and dispersed into St Augustine. Although they were Greek Orthodox in faith, they did not build a parish. The second was the arrival of Russian Orthodox monks in 1794 at Kodiak Island in Russiancontrolled Alaska. An important member of the group was the monk Herman (c. 1750–1836), who spent the rest of his life in Alaska and was proclaimed a saint of the Orthodox Church in America in 1970. These monks were sent to minister to the Russian traders in Alaska. With a missionary spirit, the monks also began to work among the Native American population, translating and creating new texts in Native American languages. These missionaries travelled as far south as today's Fort Ross in Sonoma County, California, by the 1820s. A key figure was Innocent Veniaminov (1797–1879), later elected Metropolitan of Moscow and proclaimed a saint of the Russian Orthodox Church in 1977, who organised the communities, establishing a diocese of the Russian Orthodox Church for Alaska.

However, it was not until the late nineteenth and early twentieth centuries that Orthodox parishes began to be established in the mainland USA. As immigrants arrived and pursued economic opportunities across the country, they began settling in the major cities. The Greeks were the largest of the groups, and between 1862 and 1922 they had established 141 parishes. The first were founded in Galveston, Texas; New Orleans, Louisiana; New York City; Chicago; Boston Lowell, Massachusetts; Philadelphia; Newark, New Jersey; Birmingham, Alabama; San Francisco; and St Louis. The first Antiochian Orthodox parish was established in 1895 by Father Raphael Hawaweeny (1860–1915) in New York City. Hawaweeny would go on to become the first Orthodox bishop ordained in the USA (proclaimed a saint in 2000). One of first Serbian Orthodox parishes was established in 1892–3, in Jackson, California.