The network said Thursday it had inked Miller to a multiyear deal for the political chat show, set to begin in January.
Miller said he would work four nights a week at 9 p.m. ET.
He spent six seasons on NBC's "Saturday Night Live" before launching his own HBO show, "Dennis Miller Live," winning five Emmy Awards. He drew mixed reviews for his work in the "Monday Night Football" booth, leaving in 2002 when John Madden was hired.
Miller, who was considered for a prime-time talk show on MSNBC last year before Phil Donahue was hired, said he was looking for work and intrigued by the CNBC idea after being approached by Jeff Zucker, NBC entertainment president.
"I have the same approach I would use if I were crossing a prison yard late at night," Miller said about his career in an interview with The Associated Press Thursday. "I zigzag to stay ahead of everyone."
He said he's looking forward to competing in the political talk realm with people like Fox News Channel's Bill O'Reilly, who Miller said "runs a good show."
Zucker said it was the next logical step in Miller's career.
"Having Dennis Miller return to the NBC family is one of the most exciting things to happen to us in years," he said.
Miller, a registered Republican, has become increasingly known for his political views. He bashed anti-war activists on a "Tonight" show appearance last spring, calling filmmaker Michael Moore a "stupid moron" for criticizing President Bush at the Academy Awards.
A few months later, Miller was the opening act at a Bush fund-raiser in California, earning him a ride on Air Force One and the president's limousine. He said of Bush's Democratic opponents: "I haven't seen a starting nine like that since the '62 Mets."
There was talk among some Republican political strategists of running Miller as an opponent to California Sen. Barbara Boxer.
CNBC President Pamela Thomas-Graham said Miller was intelligent and brought a unique perspective to issues.
"Even if people don't agree with him, they'll find what he's saying interesting," she said. "Our audience isn't looking for someone to tell them how to think."
CNBC has recently begun making moves to boost a lackluster prime-time lineup that can't match the ratings strength it had in the 1990s with Geraldo Rivera. Brian Williams' nightly CNBC newscast will end next year when Williams takes over from Tom Brokaw at NBC's "Nightly News."
Currently, CNBC airs "The Capital Report" at 9 p.m. four nights a week. Maria Bartiromo's news show has the time slot on Monday nights. Thomas-Graham said CNBC will continue to look at other programming ideas, though they won't include scripted comedies or dramas.
Miller's show will be taped each night at NBC's studios in Burbank. Terms of his deal were not disclosed.