The town at the head of the Manokin River was named for Princess Anne of Great Britain, daughter of King George II.

In the mid-18th century, the town became a market center based on the river trade and development of tobacco plantations in the area.

Enslaved African Americans were used to cultivate and process this labor-intensive crop, in addition to other farming.

Zion Memorial Church, Dr. William B. Pritchard House, Somerset Academy Archaeological Site, Teackle Mansion, University of Maryland Eastern Shore, Waddy House, Waterloo, and White Hall are listed on the National Register of Historic Places.

In 1933, a black man named George Armwood was accused of assaulting an elderly white woman.

He was removed from the Princess Anne jail by a white mob, dragged around town behind a truck, and eventually hanged.

[5] After the defeat of the French Empire at the hands of the Seventh Coalition in July 1815, emperor Napoleon I sought to flee to the United States to escape imprisonment.

According to local legends, Napoleon's brother, Jerome Bonaparte, had previously married Elizabeth Patterson, an American socialite from Baltimore, and through her the Bonapartes had connections to the American gentry, such as the King family in Beverly.

[8] The climate in this area is characterized by hot, humid summers and generally mild to cool winters.

Winters are relatively mild compared to areas to the north and northwest, but cold spells send temperatures well below freezing.

The Blizzard of 2018, for example, produced 10-15 inches of snow, temperatures in teens, and winds gusting over 40 miles per hour.