Spencer Penrose was born on November 2, 1865 in Philadelphia, Philadelphia County, Pennsylvania, United States in a distinguished family. He was a descendant of William Biddle, associate of William Penn and founder of the Biddle family in America, a great-grandson of Clement Biddle Penrose, one of the three commissioners for the territory ceded by France to the United States in the Louisiana Purchase, and a grandson of Charles Bingham Penrose, a leading Philadelphia lawyer. His father, Richard Alexander Fullerton Penrose (1827 - 1908), was an eminent Philadelphia physician, his mother, Sarah Hannah (Boies) Penrose, a descendant of the Thomas family of Maryland and the Boies family of Massachusetts. Spencer was the fifth of their seven sons. Three of his brothers achieved distinction, Boies as a United States Senator and longtime Republican overlord of Pennsylvania, Charles as a Philadelphia surgeon, and Richard A. F. Penrose as a geologist and metallurgist.