Fiorina cited differences over future strategy with the company's board.
"While I regret the board and I have differences about how to execute HP's strategy, I respect their decision," said Fiorina in a press release.
Robert P. Wayman, HP's chief financial officer, has stepped into the role of interim Chief Executive Officer, while Patricia C. Dunn, an HP director since 1998, has been named non-executive chairman.
Analysts believe the company need a new strategy that takes advantage of the different parts of the company.
"The question is whether HP needs new direction, or just a new driver," said Douglas Hayward, Senior Analyst at Ovum.
"We think it needs a new direction. Our view is that HP has a broad portfolio whose separate parts don't work well enough together. Fixing that will require changes to strategy, not just execution."
The board will begin searching for a replacement for Ms. Fiorina immediately.