In a terse statement, Chairwoman Barbara Boxer (D-Calif.) and ranking member Johnny Isakson (R-Ga.) said the Nevada senator "made the appropriate decision" to step down, and signaled that the decision limited but did not end their probe.
"The Senate Ethics Committee has worked diligently for 22 months on this matter and will complete its work in a timely fashion," Boxer and Isakson said.
Ensign's resignation takes effect on May 3, when the Senate is set to return from a two-week recess. On Friday, Nevada Gov. Brian Sandoval, a Republican, said he would appoint a new senator before then, while calling it "premature" to speculate who it might be.
Republicans expect Sandoval will choose Rep. Dean Heller, which would give the three-term lawmaker the advantage of incumbency in what both parties see as a key 2012 contest. Heller announced his candidacy in March after Ensign's decision not to wage what he said would be an ugly campaign for a third term of his own.
The Ethics Committee began investigating Ensign in June 2009. That month, Ensign acknowledged his affair with campaign aide Cynthia Hampton. The disclosure was prompted by her husband, Douglas Hampton — an employee in Ensign's Senate office — who had threatened to go public.
The senator later acknowledged that his parents had paid the Hamptons $96,000 after Douglas Hampton left his job in the senator's office. Ensign called the payment a gift, but critics called it an improper campaign contribution.
With his resignation, the committee loses its ability to prosecute Ensign for violations of Senate ethics rules. But the committee's work continues until it votes to end the probe, and it can forward its findings to legal authorities if it finds evidence of criminal wrongdoing.
The Justice Department had cleared Ensign of wrongdoing, but Douglas Hampton is under indictment on charges of violating federal lobbying rules.