Taylor-Brown, 25, who was born in Manchester but lives and trains in Leeds, raced to victory to strengthen her bid for a first world title having finished third in the World Series and second here in Leeds last year.
Wetherby's Jessica Learmonth held off a determined burst from Taylor Spivey of the United States to claim third and her first World Series podium in Leeds.
Katie Zaferes, the reigning world champion and current World Series leader finished second.
Five British athletes were in the top 10.
Taylor-Brown said: “It’s not properly sunk in Yet. It was amazing. The crowds were incredible and they definitely got me through that.“Right now though it hurts, my lungs are on fire.”
Learmonth added: “I’m delighted with third. When I started I thought what a day, I messed up T1 and didn’t think it was going to be my day, but I’m delighted to get through and first time on my podium in Leeds."
In the men's race, Jake Birtwhistle of Australia was also a first-time winner while Matt McElroy of the United States beat Spain's former world champion Javier Gomez into second in Millennium Square.
The Brownlee brothers of Leeds, Alistair and Jonny, despite animating the cycle race with breaks, saw their lack of race distance fitness catchh up with them as they were dropped early on the run.
Gomez said: "This course is brutal but I'm happy with third."