Defending champion Rob Cross, seeded number two, launches his title defence against American number one Danny Lauby.
Cross arrives with plenty of momentum, having lifted the Dutch Darts Masters in January.
"I'm absolutely buzzing to be here," Cross told the PDC.
"Danny is a great darts player. I've had a lot of family time recently, I feel fresh, and I'm ready to go."
World number one Luke Humphries opens against former Grand Slam quarter-finalist Stowe Buntz.
Humphries, who secured his maiden World Series title in New Zealand last year and is fresh off winning the Premier League, underlined the occasion's significance: "This is the one that every player wants to win.
"It's such an iconic venue, so for me to put my name on that trophy would mean a lot to me.
"I've got plenty of goals I want to achieve this year, but I’m fully focused on this weekend and getting back in the winner's circle again."
Teenage phenomenon Luke Littler, reigning World Series Finals champion, begins his campaign against Tour Card holder Jules van Dongen.
Brimming with assurance, Littler told the PDC he was up for the fight
"I'm feeling very confident," the 18-year-old said.
"It's great to be back. Darts is getting bigger in the States so I'm sure it’s going to be a great atmosphere.
"I've had a holiday with the family in Spain, but now I'm here I will get some practice in before tomorrow, and hopefully I can kickstart the second half of the season with a win."
Michael van Gerwen makes his competitive return following a five-week hiatus, facing Leonard Gates. The Dutchman, a two-time US Masters winner (2017 and 2023), signalled his intent:
"I love coming here," Van Gerwen said.
"I've got a great record in the US as well, so being back on American soil feels like home," admitted Van Gerwen.
"Everybody knows I've been going through really tough times, but I'm dealing with it and I'm living by the moment.
"I'm here to win, but I also need to be realistic. I've never been in this situation where I've had so many weeks of not playing competitive darts, but my head still says I need to smash them!
"I'm probably going to have a new shirt, new darts, everything. It's going to be a new Michael. Michael 2.0."
Elsewhere, 2019 champion Nathan Aspinall meets Canadian number one Matt Campbell with a potential quarter-final tie against Littler on the horizon. Gerwyn Price - runner-up in 2024 - starts against CDC Order of Merit leader Adam Sevada.
Top seed Stephen Bunting, a World Series winner in Bahrain and Copenhagen this year, takes on qualifier Jason Brandon on his US Masters debut. Australia's number one Damon Heta faces Canadian veteran Jim Long in the tournament's opening match.
Saturday's action also includes the bet365 North American Championship, where eight regional contenders fight for a place at this year's World Darts Championship and Grand Slam of Darts.
Notable ties include Campbell versus Brandon, Lauby against Gates, and a rematch between van Dongen and Buntz. Long and Sevada complete the quarter-final line-up.