Affleck will kick off the series' 30th season Oct. 2, with rapper Nelly set as musical guest, New York Daily News said.
Affleck reportedly got the hosting gig after "SNL" producers were unsuccessful at wooing Clinton to the spot, although the former U.S. president's recent heart surgery would have now prevented him from the job.
The Boston actor, who spent the summer stumping for the Democrats, emerged as a political figure during the Democratic National Convention.
Affleck's strong political beliefs and his string of failed films likely will provide the "SNL" writers with plenty of fodder for the season opener.
The actor, who last appeared on "SNL" last March, currently is promoting his upcoming film, "Surviving Christmas," with James Gandolfini and Christina Applegate.