Born in Bordeaux, Girard subsequently immigrated to the Thirteen Colonies where he established himself in the American banking industry.

Eventually accumulating a large estate which included a slave plantation in Louisiana, a 2007 article in Fortune Magazine estimated that he was the fourth-richest American in history.

[1] Having no children, Girard devoted much of his fortune to philanthropy, in particular the education and welfare of orphans, and his estate continues to fund philanthropic endeavors in the present day.

In 1760, he travelled to the colony of New York as a cabin boy and stayed there, working in the coastal trader system along the east coast and as far south as the Caribbean.

In May 1776, after the outbreak of the American Revolutionary War, Girard sailed into the port of Philadelphia to avoid a group of Royal Navy warships and settled there, running a grocery and liquor shop.

[4] In 1783, Stephen's brother John Girard left him with a slave, a woman in her twenties named Hannah, during a visit from Saint-Domingue.

[5]:89-91 Pennsylvania's 1780 Act for the Gradual Abolition of Slavery had many loopholes and although it was amended throughout Girard's life, Hannah remained his slave until his death in 1831.

The child, baptized with the name Mary, died a few months later while under the care of Mrs. John Hatcher, who had been hired by Girard as a nurse.

He supervised the conversion of a mansion outside the city limits into a hospital and recruited volunteers to nurse victims, and personally cared for patients.

[4] After the charter for the First Bank of the United States expired in 1811, Girard purchased most of its stock and its facilities on South Third Street in Philadelphia, and reestablished it under his direct personal ownership.

[5]: 249–250  Philadelphia banks balked at accepting the notes that Girard issued on his personal credit and lobbied the state to force him to incorporate, without success.

Twenty years later, his remains were re-interred in the Founder's Hall vestibule at Girard College behind a statue by Nicholas Gevelot, a French sculptor living in Philadelphia.

[13] He bequeathed nearly his entire fortune to charitable[14] and municipal institutions of Philadelphia and New Orleans, including an estimated $6 million (approximately $171 million in 2023) for establishing a boarding school for "poor, male, white orphans" in Philadelphia, primarily those who were the children of coal miners, which opened as Girard College in 1848.