William Kissam Vanderbilt I was born on December 12, 1849, in New Dorp, Staten Island in New York. His parents were Maria Louisa Kissam (1821–1896) and William Henry Vanderbilt (1821–1885), the eldest son of Commodore Cornelius Vanderbilt, an heir to his fortune and a prominent member of the Vanderbilt family who was the richest American after he took over his father's fortune in 1877 until his own death in 1885.
He was the third of eight children born to his parents. His siblings were Cornelius Vanderbilt II (1843–1899), Margaret Louisa Vanderbilt (1845–1924), Emily Thorn Vanderbilt (1852–1946), Florence Adele Vanderbilt (1854–1952), Frederick William Vanderbilt (1856–1938), Eliza Osgood Vanderbilt (1860–1936) and George Washington Vanderbilt II (1862–1914).
Vanderbilt inherited $55 million (equal to about $1.7 billion today) from his father. He managed his family railroad investments. In 1879, after taking over P. T. Barnum's Great Roman Hippodrome which was on railroad property by Madison Square Park, he renamed the facility Madison Square Garden.

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