A delicate child, Benjamin was educated by his mother and sisters and at Reverend Frederick Hatch's school. He was a student at the University of Virginia when his grandfather died on July 4, 1826, but the family's financial difficulties soon caused him to leave college. By 1829, he was back at the University studying medicine. He was elected three times as the University's prize essay writer. The Jefferson Society also elected him as a member, and Dr. Robley Dunglison considered him best in his class. He graduated on July 18, 1831.
Dr. Randolph moved to Halifax County near Danville, then to the Church Hill neighborhood in Richmond before he moved back to Albemarle County. He courted Sally Champe Carter, and they were married on November 13, 1834. They received 642 acres of land adjacent to Redlands, the estate of Sally's parents. It was here on the side of a small mountain near Carter's bridge where they built their estate named "Sharon," later renamed "Round Top." Dr. Randolph was a physician and farmer and interested himself in public affairs. He became a magistrate in 1846 and served for eighteen years. He was also a state senator from 1853-1856. Benjamin and Sally Randolph had three children: Isaetta (March 24, 1836), Lewis (June 13, 1838), and Robert (April 15, 1851).
Benjamin Randolph was a strong supporter of secession and the Confederacy during the Civil War. His son Lewis and his son-in-law served in the Confederate Army. Early in 1867, Dr. Randolph suffered a severe illness and he never fully recovered. He died on February 18, 1871, and was buried in the graveyard of Christ Church, Glendower, near Keene in Albemarle County.