The race has massive implications for the battle for the U.S. Senate.
If they win either chamber, much of President Donald Trump's agenda could be hamstrung and his administration would be subjected to greater scrutiny.
Friday night was the first debate for Cruz and O'Rourke.
In Cruz's Senate career, he has missed 13.4 percent of votes, compared to O'Rourke 2.9 percent absence for House votes over the same period. And that's a big deal in a state where a Democrat has not won a statewide election since 1988.
The debate will be a major test for O'Rourke, a former member of a punk rock band who has become a cause célèbre for many Democrats who believe he can be an effective messenger for progressive policies like marijuana legalization and raising the minimum wage.
As for Cruz, his campaign continues to worry about competing with O'Rourke financially and whether Republican voters will turn out in numbers to ensure his victory.
On the topic of President Trump, Cruz said O'Rourke wants to impeach the president.
O'Rourke's candidacy has generated widespread enthusiasm among national Democrats, but his chances of defeating Cruz, one of the GOP's most high-profile and controversial figures, remain unclear.
A question about the shooting of 26-year-old Botham Jean pivoted into Cruz chastising O'Rourke for calling for the officer's firing, using hateful rhetoric and "turning people against the police". "I think this is by design for the O'Rourke campaign, they've wanted to create that visual sense that they are making inroads in hostile territory", Wilson added. "No one here, including myself, has suggested anyone should be doing that", he said.
O'Rourke later walked back his statements and called the proposition "artless, and even inaccurate" in his 2011 book titled "Dealing Death and Drugs: The Big Business of Dope in the US and Mexico".
"The challenge for O'Rourke is to show that he is more than just a charisma candidate, that he's more than just a pretty face or an empty suit, that he really does have command of the policy issues", Wilson said. He could remain at odds with the president, which Mr. Cruz said would have been selfish and a disservice to his constituents, or he could join Mr. Trump in passing legislation like the tax overhaul that Mr. Cruz repeatedly credited with jumpstarting the economy so that "Texans lives are better". O'Rourke has publicly called for Guyger to be fired.
"The high-velocity high-impact round from an AR-15 will blow a hole the size of an orange out your back", O'Rourke said.
"The alternative, as Senator Cruz has proposed, is to deport 11 million people from this country", O'Rourke said.
"I don't buy into the labels", he replied.