The spot casts Cruz as extreme and ends with text on the screen that argues the presidential candidate is more "dangerous" than Republican front-runner Donald Trump.
"If you think Donald Trump is dangerous," reads the ad. "Watch out for Ted Cruz."
The ad, although only online for now, is a shift for the pro-Clinton group that raises money to benefit Clinton's candidacy. While the group has gone after Republicans in the past, this is the first time they have dedicated an ad to one candidate, though Priorities USA has also singled out Trump in their messaging. Around the December GOP debate, the group sponsored a filter on the social media platform Snapchat that urged event attendees to "Dump Trump."
The Cruz campaign did not immediately respond to a request for comment.
Cruz's chance of becoming the Republican nominee has grown in recent weeks. Cruz is vying for front-runner status in Iowa alongside Trump, buoyed by support from a number of top evangelical Christians in the Hawkeye State.
Titled "Cruz Control," the ad hits the senator for pledging to "prosecute Planned Parenthood" and for claiming that he believes Social Security is the "definition of a Ponzi scheme."
The ad is also an example of Democrats trying to tie other candidates to Trump, the national Republican front-runner who has scrambled the GOP race. Some Democrats have worried Trump, who is getting media considerable attention, is overshadowing other comments Republican candidates have made.
"Donald Trump may get all the attention but Ted Cruz is the GOP front-runner in Iowa and he's so extreme that he might even be worse than Trump," said Justin Barasky, communications director at Priorities USA.
It is not only Clinton's outside groups that have gone after Cruz. Clinton herself knocked the senator on foreign policy in a speech late last year by arguing "shallow slogans don't add up to a strategy."
"Promising to carpet bomb until the desert glows," Clinton said, "doesn't make you sound strong, it makes you sound like you're in over your head."