A month before voters across the country go the polls in mid-term elections that will determine the control of Congress, Mr Masters laid into incumbent senator Mark Kelly, accusing him and Mr Biden of letting inflation surge out of control and failing to lock-down the nation’s borders.
At times, particularly in the first half of the debate when Mr Masters appeared to have the momentum, Mr Kelly was saved by the intervention of Libertarian Mark Victor, who often denounced both Republicans and Democrats and claimed he had better ideas than both.
“I want to speak up on behalf of the drunken sailor,” he said at one point, in what was likely the most memorable quote of the evening.
Mr Masters 36, who is backed by tech billionaire Peter Thiel, said in his opening remarks: “Two years ago Mark Kelly stood right there and he promised to be independent. But he broke that promise.”
Mr Kelly, 58, a former Naval officer and astronaut, and the husband of former congresswoman Gabby Giffords, said the Republican held views that were “dangerous” for Arizona.
“He celebrated when Arizona enacted a national ban on abortion. And he wants to privatise your Social Security,” he said.
The event on Thursday in Phoenix will be the only major debate held in Arizona this election cycle.
The competing Senate candidates agreed to a single evening, while the debate for governor has been largely meaningless after Democratic candidate and current secretary of state Katie Hobbs said she would not appear with Republican opponent Kari Lake, who has repeated falsehoods that the 2020 election was rigged.
Polls show the Senate race very close, with Real Clear Politics curating an average of around four points advantage to Mr Kelly.
But other polls have suggested the race is all but tied, and with the Senate divided 50-50 – with vice president Kamala Harris possessing a tiebreaker vote – Republicans would love to bag Arizona and in doing so win the upper chamber. Two years, ago Mr Biden managed to become the first Democrat to win there since Bill Clinton in 1996, but he beat Donald Trump by just 10,000 votes.
On a state that borders Mexico, immigration is a key issue. Mr Masters hammered away at Mr Kelly, blaming him and Mr Biden for allowing record number of migrants to enter the country.
Records show the border authorities are set to make more than 2.3 million arrests during the 2022 fiscal year. That will exceed last year’s record of more than 1.7 million arrests.
Mr Kelly sought to place space between his actions and those of Mr Biden.
“When the president decided he’s going to do something dumb on this and change the rules and create a bigger crisis, I told him he was wrong,” Mr Kelly said.
Mr Masters retorted: “We have a wide open southern border, so if that’s the best you can do, I respectfully request you resign.”
Mr Masters had previously repeated Mr Trump’s falsehoods that the 2020 election was rigged. He also backed a very conservative position on abortion.
After winning the Republican primary and seeking to moderate his image for the kind of suburban voters he would need to win to his side, Mr Masters changed his website. Around one-third of registered voters in Arizona are independents.
On Thursday he was confronted about these changes by the moderators.
“I encourage people to go read my website now it is still the most pro life most detailed agenda of any Senate candidate running nationwide. I’m pro life. I’m proud to be pro life. I will never run from that,” he said, dodging the question.
He was also asked if he recognised Mr Biden as the president.
“Joe Biden is absolutely the president. I mean, my gosh, have you seen the gas prices lately,” he replied.
He was asked if he thought the election was “rigged”.
“I suspect that if the FBI didn’t work with big tech and big media to censor the Hunter Biden infer or the Hunter Biden crime story,” he said.
“I suspect that changed a lot of people’s votes. I suspect President Trump would be in the White House today, if big tech and big media and the FBI didn’t work together to put the thumb on the scale to get Joe Biden in there.”
Mr Kelly also landed some blows.
Looking at Mr Masters, he said: “I think we all know guys like this - guys that think they know better than every one about everything.”
He added: “You think you know better than women and doctors about abortion. You even think you know better than seniors about Social Security, and you think you know better than veterans about how to win a war.”
He said: “Folks, we all know guys like this. And we can’t be letting them make decisions about us. Because it’s just dangerous.”