The mouth of the St. Joseph River at present day St. Joseph was an important point of Amerindian travel and commerce, as it lay along a key water route between the Great Lakes and the Mississippi River. Both the Miami and Potawatomi used this route and would use the area as a camp. The St. Joseph River also allowed for connection with the Sauk Trail, which was the major land trail through Michigan. In 1669, the mouth of the river was discovered by European explorers. French explorer René-Robert Cavelier, Sieur de La Salle, built Fort Miami on the bluff overlooking Lake Michigan. In 1679, he waited for the ship Le Griffon, which never returned. Once the ship was deemed lost, La Salle and his men made the first land crossing of the lower peninsula by Europeans.
The next permanent white settler in St. Joseph was William Burnett, who around 1780 started a trading post at the mouth of the St. Joseph River. The post traded food, furs and goods with places including Detroit, Mackinac and Chicago. In 1829, Calvin Britain, who had come from Jefferson County, New York, and had taught at the Carey Mission at Niles for two years, came to the site of St. Joseph. Shortly thereafter, he laid out the plat of the village, then known as Newburyport, named after a coastal city in Massachusetts. Britain was influential in attracting other settlers to the area. Lots sold rapidly and the village flourished.
The St. Joseph river mouth was straightened through a channel and piers were added later. The first lighthouse in St. Joseph contends with Chicago's original lighthouse as the first to be built on Lake Michigan. Newburyport changed its name to St. Joseph when it was incorporated in 1834.
The first water route across Lake Michigan between St. Joseph and Chicago began as a mail route in 1825, but service was sporadic until 1842 when Samuel and Eber Ward began a permanent service. That lasted eleven years. Before the rise of large ship companies on Lake Michigan, service was done primarily by owner-operated boats. With the rise in shipping in Benton Harbor and the rise in tourism in St. Joseph, permanent and larger operations began operating out of the ports.