Slave trade
After the war, DeWolf was selected as captain of a ship in his 20s. He began to engage in commercial ventures, including slave trading, often purchasing seasoned slaves from Cuba and other ports in the West Indies and transporting them primarily to southern markets in the United States. Although Rhode Island outlawed slave trading in 1787, DeWolf and his family continued to finance and command slaving voyages to West Africa.
In 1791, DeWolf was indicted for murder by a grand jury in Newport, Rhode Island. The case was widely reported in the New England press. He was alleged to have directed the murder of a female African slave in 1789 who was sick with smallpox on the ship Polly, which he commanded; after having been treated to the best of the crew's knowledge, she was bound to a chair and lowered overboard. Such cases were known at the time, as all the persons on a ship were threatened in cases of severe disease outbreaks. The judge in charge of the case ultimately accepted the prosecuting attorney's filing of nolle prosequi, a formal declaration "that he did not wish to pursue the case." When DeWolf had heard of the indictment, he had immediately left for the Gold Coast of Africa.
DeWolf was later charged in the case in Saint Thomas, where he was then living. Two members of the crew, one of whom had taken part in the murder, as he had already had smallpox and was considered immune, said in a 1794 deposition taken in St. Eustatius, Leeward Islands, that the slave had to be thrown off in order to save the remainder of the slaves and crew from the infectious disease. This was justifiable according to contemporary maritime law. In 1795 DeWolf testified about the case in court in Saint Thomas, West Indies, with no one present to oppose his testimony; the Danish judge ruled in his favor.
DeWolf financed another 25 slaving voyages, usually with other members of his family. His father and uncle Simeon Potter were slave traders since 1769. His nephew George DeWolf kept it up illegally until 1820. In total, the DeWolf family is believed to have transported more than 11,000 slaves to the United States before the African slave trade was banned in 1808.
James DeWolf also owned a rum distillery for use in trade in West Africa, and with his brothers and nephews started the Bank of Bristol, with two generations of family, and an insurance company, which together financed and insured their slave ships. From 1805 to 1807, their Mount Hope Insurance Company insured 50 slaving voyages. A family member established a slave auction house in Charleston, South Carolina, the destination for many of their slave ships.