The community was founded on a portion of the 1,000 acres of Survey No. 418 of the Virginia Military District purchased by Colonel James Poage of Staunton, VA. Poage was determined to live in a free state and settled on his claim as early as 1804. His anti-slavery views attracted other souther abolitionists to the area. Ripley was incorporated as the village of Staunton in 1812, and the name was later changed to honor Brigadier General Eleazar Wheelock Ripley for his efforts in the War of 1812.
Located 50 miles upriver from Cincinnati, during the 19th century Ripley was one of the great Ohio River shipping points in southern Ohio. This was an important commercial river port during the steamboat and flatboat eras.
Today the village's large historic district includes buildings dating back to the early 19th century, with several homes, particularly on Front St., having once belonged to residents who were active "conductors" on the Underground Railroad. Monuments erected during the village's Centennial Week in 1912 commemorate Ripley's noted abolitionists and "railroaders."