"During my time in Congress, I have always acted in an ethical manner within the rules of our body and the laws of our land," the Texas lawmaker told fellow Republicans in a letter informing them of his decision.
Still, referring to criminal charges he faces in his home state, he added, "I cannot allow our adversaries to divide and distract our attention."
DeLay temporarily have given up his leadership post after he was charged, but always insisted he would reclaim his duties after clearing his name.
His turnabout cleared the way for leadership elections among Republicans buffeted by poor polls and by lobbyist Jack Abramoff's confessions of guilt on corruption charges in connection with congressional wining and dining.
Earlier this week, former House Speaker Newt Gingrich told the CBS Evening News that
"As a practical matter, he can't go through this whole process and be an effective leader," Gingrich said.
Speaker Dennis Hastert, his own grip on power secure, said he expects elections to be held when lawmakers return to the Capitol the week of Jan. 31. That set the stage for several weeks of political maneuvering, and the possibility of a wholesale shuffle in the leadership lineup 10 months before midterm elections.
There's no shortage of candidates lining up to replace DeLay, but there is no one else like him – a brash, often-uncompromising conservative, reports CBS News correspondent Gloria Borger.
Democrats, eager to take control of the House in November, reacted to DeLay's announcement with studied indifference.
"The culture of corruption is so pervasive in the Republican conference that a single person stepping down is not nearly enough to clean up the Republican Congress," said Rep. Nancy Pelosi of California, the Democratic leader.
Added Rep. Rahm Emanuel of Illinois, chairman of the House Democratic campaign organization: "With the permanence of their special interest philosophy, a change in the Republican cast of characters simply doesn't matter."
Democrats must gain 15 seats in November to win control of the 435-member House.
Missouri Rep. Roy Blunt, the GOP whip who has been acting as majority leader while DeLay fights his own legal battle, signaled he intends to run for majority leader.
Ohio Rep. John Boehner, once a member of the leadership, was expected to make a formal announcement on Sunday.