The ad, which will launch Thursday and air for a week in Louisville and Lexington, Ky., is a soft spot in which Chao speaks directly to the camera, defending her husband's commitment to the state.
"You've seen the ads attacking my husband. As Mitch McConnell's wife, I've learned to expect them. Now far-left special interest are also attacking my ethnicity, even attacking Mitch's patriotism, because he's married to me. That's how low some people will stoop," she says.
She goes on to add that McConnell "works his heart out to protect Kentucky from Washington's bad ideas, because Mitch loves Kentucky."
"We love Kentucky. The meanest personal attacks can never change that," she says.
Chao is referencing a controversial tweet sent by liberal super-PAC Progress Kentucky that referenced Chao and suggested her relationship with McConnell "may explain why your job moved to #China!"
The tweet drew condemnation from Republicans and Democrats alike, and Progress Kentucky eventually apologized and deleted it.
And the Democratic Senatorial Campaign Committee, in a release issued by spokesman Matt Canter, again disavowed the tweet.
"We strongly disagree with the tweet that Mitch McConnell is referencing in his new ad, but let's be honest: Mitch McConnell is not a victim. In fact, he is the reason for Washington's dysfunction," he said.
The ad is backed by a six-figure buy and will run online as well. Watch: