Josephine Louise Le Monnier was born in Baltimore on October 31, 1816 to Mary Sophia Waters and Alexander Le Monnier. She received her education in Baltimore and in her father's native France. After her mother died, Le Monnier went to live in New Orleans, where her older sister Eleanor Anne and brother-in-law William Henderson had settled. There, Le Monnier met Warren Newcomb, and the couple married in Christ Church Cathedral on December 15, 1845.
The couple moved to Louisville, Kentucky, and had a son, Warren, Jr., who died shortly after his birth in 1853. The couple later moved to New York, where Josephine gave birth to their second child, Harriott Sophie Newcomb, on July 29, 1855.