From September 1864 to February 1865, this site was the location of one of the largest prisoner-of-war camps in the country during the Civil War (1861-1865). Called the Florence Stockade, it was a Confederate camp and between 15,000 and 18,000 Union troops were imprisoned here. The camp was rectangle in shape at 1,400 feet long and 735 feet wide, encompassing an area of 23.5 acres. The walls were built using vertical timbers sunk into the ground and each corner had a raised platform for artillery. Confederate guards manned an earthen rampart that surrounded the walls on the outer side. A ditch surrounded the entire camp, which was an open stockade; there was no shelter. Like at all prisons during the war, the troops imprisoned here suffered greatly from the weather, lack of food, disease and poor sanitation. As a result, around 2,800 died. Today, the site features a parking area, a gazebo with interpretive signs, and an interpretive walking trail.

The land that was used to create Florence National Cemetery was appropriated, and later purchased, from the estate of a local resident who lived in the vicinity of a prisoner of war camp operated by the Confederate military. Original interments were made in two separate burial grounds, one containing 416 Union veterans. The second contained the remains of approximately 2,322 soldiers who perished in the Confederate prisoner of war camp. Interments at the larger site were made in 16 trenches. In 1865, this site was designated as a national cemetery and the remains from the smaller burial ground were reinterred withing the boundaries of the present location. Remains were also disinterred and moved to the cemetery from the surrounding region. The original wooden headboards marking the trench graves were replaced by 2,167 marble "unknown" head blocks measuring 6 x 6 inches square and set approximately six inches apart. In 1955, all but five of these markers were replaced with 32 upright marble headstones at each end of the trenches.

Although no longer used for its original purpose, the former Florence Public Library remains an important landmark in Florence. Constructed in 1925, the building was home to the city's first public library and is an excellent example of Classical Revival architecture. Designed by architect William J. Wilkins and Frank V. Hopkins, notable features include a large arched main entrance, arched windows with keystones, and limestone decorative elements. A law office occupies the building today.

Now an adult education center, the former Poynor Junior High School is the oldest school building still standing in Florence County. It was built in 1908 and has remained an important landmark for the city ever since. It is also an excellent example of Georgian Revival architecture and features a large portico with Ionic columns. It was added to the National Register of Historic Places in 1983.

The Florence County Museum preserves and interprets the history and culture of east-central South Carolina through exhibits and programs. The museum is best-known for the Wright Collection of Southern Art, which has over 140 pieces from various 20th century artists. Other highlights include a collection of works from Harlem Renaissance artist William H. Johnson and a famous original painting of Revolutionary War hero Francis Marion crossing the Pee Dee River. The museum also has various lectures and programs available for all ages or education levels.

The former U.S. Post Office remains one of the city's most attractive and historic buildings. Built around 1906, it is significant for its architecture and association with the federal government, which operated the post office. The building also housed a federal court and government offices, including the office of a U.S. congressman. In terms of design, the building is a fine example of Second Renaissance architecture. It features a wide, projecting cornice, segmentally arched and pedimented windows, and "eye of bull" dormers on the roof. The building appears to currently house a variety of offices.