The first million-dollar business in the U.S. was likely the Virginia Company of London, founded in 1606, which funded the Jamestown settlement and profited from tobacco trade. However, the first self-made female millionaire was Madam C.J. Walker, who built a haircare empire in the early 1900s selling products for Black women. Her success made her one of the earliest and most inspiring rags-to-riches entrepreneurs in history.