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Called "Learn from Mistakes," the minute-and-a-half long ad cites two Iraqi refugees who settled in Kentucky in 2009 who later pleaded guilty to supporting terrorism.
The ad will begin airing Monday in early states Iowa and New Hampshire, ahead of the CNN-hosted GOP debate on Tuesday, according to Paul's campaign. The networks that will air the ads and size of the buy were not disclosed.
The narrator then says "some refused to learn from mistakes" as clips play of the Texas and Florida senators expressing openness to welcoming refugees. The clips imply both supported accepting Syrian refugees without condition, though both Cruz and Rubio have called for halting any program accepting refugees from Syria in the wake of the Paris terrorist attacks.
The ad goes on to paint Paul as tougher on national security.
"Rand Paul sounded the alarm," the voice over says, as a clip plays of Paul on Fox News saying he opposed the Gang of Eight immigration bill Rubio helped author.
"Rand Paul wrote the amendment to suspend visas to nations with high risks of terrorism, but Marco Rubio voted no," the narrator says.
Paul has called for not just scrutinizing refugees, but disallowing easy access to any visitors to the U.S. with ties to at-risk regions.
The Kentucky Republican has struggled to gain traction in the polls and has hovered in the low single digits for months. Cruz and Paul, meanwhile, have been cementing spots among the top four candidates in recent weeks.
Foreign policy has been an area setting Paul apart from the field since the beginning of his campaign. A libertarian-leaning Repubilcan, Paul favors a more isolationist policy than his colleagues, and in the last presidential debate got into a heated argument with Rubio over military spending. Paul advocated for cutting military spending with overall government spending, hitting Rubio for wanting to increase defense dollars.