The resignation was expected after he was named the Congress candidate from Bangalore South.
Nilekani said: "I am resigning as of today." He said that he had given his resignation to the Prime Minister.
Nilekani formally joined the Congress on Sunday and will be pitted against BJP's Ananth Kumar.
Bangalore South has been a hostile terrain for Congress which had been tasting defeat since the late 1970s, barring in 1989 when former Chief Minister late R Gundu Rao had won.
Weeks before his formal entry into Congress, Nilekani had begun his campaign facing a daunting task to reach out to 20 lakh plus voters.
Recently, Karnataka BJP had petitioned electoral authorities against Nilekani, taking exception to his name and picture figuring with Aadhar card advertisements, when the Model Code of Conduct is in force.
With PTI inputs