He was for a time active in the management of the family railroads, though not much after 1903. His sons William Kissam Vanderbilt Jr. (1878-1944) and Harold Stirling Vanderbilt (1884-1970) were the last to be active in the railroads, the latter losing a proxy battle for the New York Central Railroad in the 1950s.
William K. Vanderbilt's first wife was Alva Erskine Smith, who he married in 1875. Born in 1853 to a slave-owning Alabama family, she was the mother of his children and was instrumental in forcing their daughter Consuelo (1877-1964) to marry the the 9th Duke of Marlborough in 1895. Not long after this the Vanderbilts divorced, William K. later marrying Anne Harriman Rutherford Sands and Alva marrying Oliver Hazzard Perry Belmont.
His homes included Idle Hour (1900) on Long Island, New York and Marble House (1892), designed by Richard Morris Hunt who also designed his 660 Fifth Avenue mansion (1883), in Newport. He died in Paris in 1920. He was buried on Staten Island where he had been born.