In 1857 the Savannah, Albany and Gulf Railroad Company's line from Savannah, Georgia to Screven (then known as Station Seven) was completed when then trestle was built over the Altamaha River at Doctortown. Prior to this, the tracks connected the town to Thomasville, then a popular resort destination for wealthy Northerners and Europeans. The town was named for Dr. James Proctor Screven of the Atlantic and Gulf Railroad. After Dr. Screven's death in 1859, his son John Bryan Screven took over the railroad and continued its development. Both men served as mayor of Savannah. A section of the tracks just outside Screven on the Little Satilla is still known as the Abutment, the name it was given during the construction of the tracks.
The town was originally in the 4th land District of Appling County and moved into Wayne County when the county lines were redrawn after the American Civil War ended. The Confederate States Army had a training camp, Camp Harrison, in Screven for a short time in the Fall of 1860. The soldiers came by train to Screven.
Following the Civil War, Captain Christopher Columbus Grace, one of the Immortal 600, came to Screven and established himself in the turpentine, ginning and trade store business. In 1877, he erected a sawmill that spurned the community's growth. In 1880, he was a founding member of the Screven Methodist Episcopal Church, the first church established in the town of Screven. Other men of commerce came to join Captain Grace in the town of Screven. J. A. Hilton building the community's first brick store and operated a hardware store in later years. The J. H. Walker Company opened a mercantile business in 1876 and J. C. Hatcher opened a store in 1899. In the mid-1890s, the Royal family relocated to Screven to work with the Atlantic Coastline Railroad.
Railroad history was made on Screven's tracks in March 1901 in an event that still holds forth in railroad lore. The Spanish–American War had ended, but occupation troops were to remain in Cuba until 1902. Post Office Department officials, realizing the need for faster mail service, had begun drawing up a contract to award to either the Plant System (then known as the Savannah, Florida and Western) or the Seaboard Air Line Railroad, both of which operated south of the ACL termination point of Charleston, South Carolina. The Havana mail would depart from Jacksonville. Actually, Seaboard was favored because of her more direct route. The Plant Road detoured over 30 miles from Savannah to Waycross then to Jacksonville. And it was Jacksonville where the steam packet to Havana waited to load the mail. Both trains left Union Station in Savannah at 3:00 a.m. The SF&W's route was a longer one since it traveled through Jesup, Screven, and Waycross before cutting over southwest to Folkston to travel on to Jacksonville. Twelve miles out of Savannah, the SF&W’s engines ran hot. After one attempt at repairing the engine failed, Engineer Albert Lodge made the decision to switch engines and start again making it from Fleming to Jesup in less than 33 minutes. Knowing he must make up an hour of time if they were to have a shot at the mail contract, Lodge ripped out of Jesup on Number 111 and made 11 miles in 9 minutes. More speed was added and the train traveled five miles in two and a half minutes – she was traveling at 120 miles per hour when she passed through the town of Screven and approached the Little Satilla Bridge. Dispatcher D. S. McClellan is quoted as saying, "I shall never forget the things that passed through my mind as this train reached the top of a little hill just south of Screven and started slowing down for the fill for the Satilla River. There is a little curve just after passing over the river, and I wondered if the engine were going to take that curve or if it were going to take to the woods." When the train came into Waycross, the crew figured they had come the 40 miles from Jesup in 28 minutes. The stop in Waycross completed, the train headed south to Racepondand arrived in Folkston in 25 minutes. Engine 111 arrived in Jacksonville at 6:31. The men had traveled faster than any other and their record would stay unequaled until 1934; to date, it has never been beaten.
Country schools dotted the landscape in and around Screven and the present school building is used for grades pre-k through five. The school was relocated to this location from an area around the old Screven fire department in the early 1920s. The upper building housing the pre-kindergarten classes and the office suite were built in 1922. A Works Progress Administration construction crew constructed the auditorium and middle building as a part of Franklin Delano Roosevelt's New Deal legislation in 1936–1937 when P. D. Griffis was the chairman of the Screven Board of Education. This same WPA crew built the Jesup Post Office (now Jesup City Hall) and the Odum Elementary School gym and high school building. Consolidation of schools in 1966 marks the beginning of the decline in population in Screven. W.L.(Bill) Bohler was made principal of the school in 1966 and saw the school transition from a high school to an elementary and middle school(grades 1–7)and remained principal until 1972. His wife, Dorothy, was the school's math teacher for many years and was known for her progressive thinking and teaching methods. Their only son, J. David Bohler, went on to become a nationally recognized physician and scholar in South Carolina and has been quoted as saying "If not for growing up in Screven, I wouldn't be where I am today. I'm the best educated Redneck to ever come out of Georgia". Dr. Bohler has also traveled the world as a big game hunter, taking trophies including the "big five" in Africa.
Screven was once the largest town in the county because of its association with the railroad. Following the ACL's decision to locate Rice Yard in Waycross and Jesup's growth as the county seat, its population began to decline. The Grace family continued to play an important role in Screven. Captain Grace's grandson, Lindsay Grace, maintained an important presence in the town and contributed greatly to the county's economy through his business ventures. Mr. Grace helped to establish the Lake Grace recreational area between Screven and Odum. Another member of the Grace family, Robert Lindsay Thomas, a Screven farmer, served in the United States House of Representatives from 1982 to 1992 and later served on the 1996 Atlanta Committee for the Olympic Games.
In March 2005, Screven was hit by a tornado, causing the uprooting of trees, damaged homes and stores in the downtown area, and devastated Screven Cabinets into a pile of sheet metal and insulation. No one was killed, but some were trapped in their homes and businesses.
Screven is home to a former National Champion Turkey Oak tree but the tree sustained damage in a storm and is no longer the champion. The tree is located on property belonging to the Screven United Methodist Church on School Street in Screven. Screven is also home to the Southern Pride Agriculture Ride, a bike ride that starts and ends at Grace Community Center and the home of the Screven Ghost Light, a bouncing orb of light seen for over a century at the railroad crossing on Bennett Road. Those who have seen the light say it moves back and forth and glows bright and then dim. It reportedly is seen after rain and after a train has gone by. Bennett Road is located 4 miles out of Screven on Hwy 84 East.
The town celebrated its centennial in mid-2007 during the town's July 4 observance and with a community celebration on August 19.