The three-term congressman faced nominal opposition in the primary. The Associated Press declared him the winner with 68 percent vote with about a third of precincts reporting.
The general election is expected to be a nasty fight.
Melancon has already been on the receiving end of some hard-hitting ads released by Vitter. One TV spot released earlier this month accused the Democrat of supporting government benefits for "illegals" and using $50,000 to "get himself a luxury SUV."
Melancon said he expected a tough race. "That's how David Vitter runs his campaigns, but I'm not going to let him run over me," he told The Ballot Box earlier this week. "The gloves have been off but we knew it was [coming]."
One of the Democrat's weaknesses is that President Obama is unpopular in Louisiana. Vitter has positioned himself as a staunch critic of Obama and tried to tie Melancon to the controversial elements of the Democrats' agenda.
Meanwhile, Melancon was able to increase his exposure in the the wake of the BP oil spill, when he made regular appearances on cable news shows. But he'll need to improve his fundraising if he wants to compete with Vitter. As of Aug. 8, Melancon had $2.2 million cash on hand to $5.3 million for Vitter.