He inherited a fortune and enlarged it through business dealings, then devoted much of his money and efforts to a wide variety of philanthropic purposes.

Amongst his many investments, he possessed major holdings in banking, tobacco, railroads, mining and oil.

Whitney made charitable contributions to the rowing team at his alma mater, Yale University, including donating funds to build a dormitory for the crew.

[6] His will bequeathed more than $20 million to establish the Payne Whitney Psychiatric Clinic at Cornell University's medical school, now called Weill Cornell Medicine, and New York Hospital, now New York–Presbyterian Hospital in New York City.

Together, they had two children:[11] On September 20, 1911, Whitney was aboard the RMS Olympic when it was rammed by the warship HMS Hawke.