Ensign revealed his decision to abandon his leadership role during a phone conversation with Senate Republican Leader Mitch McConnell of Kentucky, The Wall Street Journal reported.
Besides being chairman of the Senate Republican Policy Committee, an elected leadership role, Ensign was chairman of the Senate Republican campaign operation for the 2008 election cycle.
On Tuesday in Las Vegas, the Nevada lawmaker announced he had an affair in 2008 and "violated the vows of my marriage. It is the worst thing I have ever done in my life. If there was ever anything in my life that I could take back, this would be it."
Ensign said the affair went on between December 2007 and August 2008 with a campaign aide married to an employee in his Senate office. The husband and wife haven't worked for the senator since May 2008.
Mr. Ensign was first elected to the Senate in 2000 and faces re-election in 2012.