The hour-long debate showcased a major shift in tone for O'Rourke, who rarely says the names of Cruz or President Donald Trump on the campaign trail and has often bypassed his opportunities to take direct shots at Cruz.
O'Rourke's comment came in response to Cruz's criticism of the Democrat's desire for a tax on oil production.
Ted Cruz is the butt of another joke, this time it's an ad aimed at the senator's appreciation for the fast food joint, White Castle, instead of Texas' Whataburger.
"It's why the President called him 'Lying Ted, ' and it's why the nickname stuck - because it's true", he said.
Cruz said. "With Congressman O'Rourke leading the way, [there'll be] two years of a partisan circus and a witch hunt on the president". During the 2016 presidential race, Trump re-tweeted an unflattering photo of Cruz's wife and suggested that his Cuban-born father had a hand in John F. Kennedy's assassination.
With Election Day just three weeks away, Tuesday might have been one of O'Rourke's last shots to gain ground.
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In a line that underscored Democratic worries that O'Rourke hasn't won over enough Latino voters, Cruz said: "The people of Texas, and I will say, especially the Hispanic community, we don't want to see taxpayer-funded, Medicaid-funded abortions".
O'Rourke "is not in the same league" as Cruz, Trump wrote, adding that Cruz has helped slash regulations and taxes and been a vigilant guardian of Second Amendment gun rights. A poll average compiled by Real Clear Politics gives Cruz a lead of 7 percentage points, and a new CNN poll published on Tuesday gave Cruz a similar margin.
O'Rourke is trailing behind Cruz in the latest polls, despite his record-setting $38 million in campaign funds last quarter.
Cruz closed by again highlighting his policy differences with O'Rourke on immigration, health care and a host of issues, saying he is also offering a positive vision for the state of Texas. O'Rourke and most Democrats opposed the measure.
O'Rourke countered that Cruz was ineffective and self-serving in the Senate, more interested in his political career than in helping Texans.
"It's really interesting to hear you talk about a partisan circus after your last six years in the US Senate", O'Rourke fired back.
Cue a clip of Cruz declaring that "I'm a big fan of eating White Castle burgers". He said he can work with the president and criticized O'Rourke for saying he's in favor of impeaching the president.