No successor has been named, but James will remain at Intel through the end of the year to help ease the transition to another executive leader.
In the wake of her departure, two groups that were under her purview -- Intel's Technology and Manufacturing Group and HR -- will report to CEO Brian Krzanich instead. The remainder of her direct reports will transition to other internal organizations.
James and Krzanich assumed their respective roles in 2013 following the retirement of former CEO Paul Otellini.
"When Brian and I were appointed to our current roles, I knew then that being the leader of a company was something that I desired as part of my own leadership journey," James wrote in a letter to Intel employees. "Now is the right time for me to take that next step."
Intel has been working to help increase diversity in the tech industry, including the establishment of a $125 million investment fund targeting startups run by women and minorities.
Waning PC sales in recent years have challenged growth at Intel, which has tried to set its sights on alternative markets such as the Internet of Things (IoT) instead. The company's mobile business has also been struggling.
Last month, Intel agreed to buy reprogrammable-chip maker Altera for about $16.7 billion in an effort to expand its server and IoT capabilities.
Other leadership changes Intel announced on Thursday include the upcoming January retirement of Arvind Sodhani, president of Intel Capital. Wendell Brooks, president of Mergers and Acquisitions, will assume that role.
The Intel Security organization, meanwhile -- which was formerly the independent McAfee division -- has been formally integrated into Intel operations under the leadership of General Manager Chris Young.
Intel Communication and Devices Group General Manager Aicha Evans has been elevated to the company's Management Committee, and Josh Walden, general manager of its New Technology Group, has been given expanded responsibilities.
Finally, executives Hermann Eul and Mike Bell will leave the company after a transition period, Intel said.