[3] Prentiss is located on the Longleaf Trace, Mississippi's first recreational rail trail.

Originally part of Lawrence County, the town was first named "Blountville", after William Blount, an early settler and merchant.

Situated on 40 acres (16 ha) of land, with remnants of slave quarters on the property, it was considered one of the finest schools for African Americans in Mississippi.

The school at first taught only the elementary grades, and began with 40 students whose tuition was often paid with chickens, eggs and produce.

A Rosenwald classroom was built on the campus in 1926, and by 1953 the "Prentiss Normal and Industrial Institute" included a high school and junior college, had 44 faculty and more than 700 students, and included 24 buildings and 400 acres (160 ha) of farmland, pasture and forest.

[8][9] Ralph Fults and Raymond Hamilton, members of the notorious Barrow Gang, robbed the bank in Prentiss in 1935.

[11] Prentiss police officer Ron Jones, Jr. was shot and killed by Cory Maye while executing a search warrant in 2001.

According to the United States Census Bureau, the town has a total area of 1.9 square miles (4.9 km2), all land.

Local attractions include: In 1993, the Canadian National Railway announced it would abandon the former Illinois Central line which ran through Prentiss.

This enabled the construction of the Longleaf Trace, Mississippi's first recreational rail trail, located between Prentiss and Hattiesburg.

[16] Detachment 2 of the 155th Brigade Combat Team of the Mississippi Army National Guard is located in Prentiss.

The Prentiss-Jefferson Davis County Airport is located 3 miles (5 km) west of the town.