Whitman will relinquish her title as president and chief executive at the auction giant on 31 March, and will remain with the company only as a member of its board of directors.
She will be replaced by John Donahoe, president of eBay's marketplaces branch, which is responsible for 70 per cent of eBay's US$7.7bn annual revenue.
Whitman leaves after nine years at the helm of eBay, which had just 30 employees and 500,000 registered users when she joined.
"With humour, smarts and unflappable determination, Meg took a small, barely known online auction site and helped it become an integral part of our lives," said eBay founder Pierre Omidyar.
Donahoe will be assisted as chief executive by PayPal president Rajiv Dutta, who will become eBay's executive vice president. Dutta will also be given a seat on eBay's board.
PayPal chief technology officer Scott Thompson will take over Dutta's position as president of the online payment service.
Meg Whitman steps down at eBay
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