The group, Kentuckians for Strong Leadership, will spend $260,000 to air an ad on broadcast and cable television in multiple markets starting early next week.
It follows a similar buy launched by Senate Majority PAC and Patriot Majority USA earlier this week, backing spots that hammer McConnell on his vote for the financial bailout and his long tenure in Congress.
A source with Kentuckians for Strong Leadership wouldn't offer further details on the contents of the ad.
But the fact that the two parties are already sparring on air reflects the fact that the race could become one of the most hotly-contested in the nation — if Democrats can front a credible candidate.
A handful of potential contenders have declined to run, and all eyes are currently on Kentucky Secretary of State Alison Lundergan Grimes. She's considered a strong recruit but still hasn't decided on running.
Democrats believe McConnell is vulnerable, citing polling that has shown him to be unpopular in his home state and below 50 percent support in a head-to-head match-up against certain potential candidates.
But McConnell's deep coffers and savvy campaign operation — he's seeking to build a presidential-level campaign, and is borrowing tactics from President Obama's reelection fight — will make him a tough incumbent to beat.