No information about Chopra's future plans or his replacement was immediately available.
Chopra was an advocate for expanding the use of technology in healthcare and making government more transparent by putting more information online.
As the president's top technology adviser, Chopra was one of three officials who wrote the administration's position on controversial online piracy legislation earlier this month. The officials said they would not support measures that stifled free speech or restricted the openness of the Internet, but they emphasized their support for giving law enforcement agents new tools to crack down on copyright infringement.
Chopra worked closely with Vivek Kundra, who as chief information officer was in charge of overseeing the federal government's information technology. Steven VanRoekel replaced Kunda as the CIO in August.
Prior to taking his post in May 2009, Chopra served as Virginia's secretary of technology.
He attended Johns Hopkins University and received a master's degree in public policy from Harvard's Kennedy School.
Obama excited Silicon Valley when he first said he planned to create a post for a top technology officer. Some speculated that Google Chairman Eric Schmidt would take the job, but he quickly shot down the rumors.
News of Chopa's resignation was first reported by FedScoop.com.
—Updated at 12:02