Levy was born on April 22, 1792, in Philadelphia, Pennsylvania to Michael and Rachel Phillips Levy. He had two older siblings. Uriah Levy was close to his maternal grandfather, Jonas Phillips, who had emigrated to the United States in 1756 from Germany, and fought with the Philadelphia militia in the American Revolution. His maternal great-great grandfather, Dr. Samuel Ribeiro Nunes, a Portuguese physician, was among a group of 42 Sephardic Jews who escaped the Spanish Inquisition of the early 16th century and migrated to England, where they settled. Descendants of that group sailed from London in 1733 and helped found the city of Savannah, Georgia, where they lived for generations.