In 2007 a consortium started the Port Tobacco Archeology Project, devoted to revealing the history of Native Americans and colonial Europeans and Africans.

It is notable as a Jesuit mission center established in the 17th century and is likely the oldest continuously operating Roman Catholic parish founded in the Thirteen Colonies.

[10] Areas along the waterways of present-day Maryland were inhabited for thousands of years by various cultures of distinct indigenous peoples.

At the time of European exploration, this coastal area along the Port Tobacco River was the territory of the Potapoco, an Algonquian-speaking tribe.

[11][12] Within a generation of the first Maryland settlers' landing at St. Clement's Island, they pushed the frontiers of the colony north and west toward the Potomac and Port Tobacco rivers.

The manor's chapel was expanded to what is called St. Ignatius Church, a center for local Native Americans converted to Christianity.

The oldest continuously operating Catholic parish in the United States, the complex has been designated as a National Historic Landmark and is part of the Religious Freedom Maryland Scenic Byways route.

[15] For two centuries, Port Tobacco area residents assumed important roles in state and national history.

[16] Due to military plans she passed to the Confederates that summer, she was credited with ensuring their victory at the First Battle of Bull Run in July 1861.

[17] Local slaves were freed following Maryland's adoption of a new Constitution on November 1, 1864 (the Emancipation Proclamation of 1863 did not apply to states which remained in the Union).

During the hunt for John Wilkes Booth after the assassination of President Abraham Lincoln, intelligence gathered in a Port Tobacco hotel (Brawner Hotel) (conspirator George Atzerodt lived in town) established the assassin had fled with his companion Herold into Virginia, where they were ultimately located and Herold surrendered, but Booth died during the attempted capture.

Port Tobacco started declining as erosion from excessive agricultural use and poor soil conservation caused significant siltation at the head of the Port Tobacco River, decreasing its navigability and ultimately cutting off the town from access to Chesapeake Bay and the Atlantic Ocean.

Larger merchant vessels were unable to use the former seaport; as a result, commercial activity at the port had dwindled by the time of the Civil War.

[19] A small portion of the town's square incorporated in 1888 as Port Tobacco Village,[7][8] a move that may have signaled an effort by the community to reverse its decline, but new communities eventually sprang up along the railway and prospered, including the town of La Plata which succeeded Port Tobacco as the county seat in 1895.

Because of the town's abrupt decline and silting of the river, many archeological sites were preserved, making it one of the richest areas for studying the mixed history of Native and colonial cultures, including that of enslaved Africans.

The North wing has exhibits on tobacco culture, as well as archaeological finds which reveal early colonial and Native American life.

By most accounts, the spirit of a large blue dog protects the treasure of his murdered master, which is supposed to be buried somewhere along Rose Hill Road outside Port Tobacco.

Charles Stuart was the owner of the Rose Hill property containing the fabled rock where Blue Dog and his master were killed.

[23] The legend says that Charles Thomas Sims, a soldier, and his dog were killed on February 8 in the 18th century on Rose Hill Road while returning from a Port Tobacco tavern.

Port Tobacco Village is located in central Charles County near the intersection of Maryland Route 6 and Chapel Point Road, just southwest of the neighboring town of La Plata.