The 25-year-old Texan overcame injury to complete a stunning free skate routine, including landing a triple Axel, to take the top spot in Chongqing.
The result added to her triumph in Angers, France, earlier in November.
Glenn, who has been praised for speaking openly about her mental health including her struggles with ADHD, overhauled Mone Chiba of Japan, who had a narrow lead after Friday's short programme.
Chiba, 19, held her head in her hands after a lapse in concentration saw her fall during the closing stages of an otherwise flawless routine. South Korea's Kim Chae-yeon took bronze.
Chiba and Glenn both placed high enough to qualify for December's Grand Prix Final in Grenoble, France, which features the world's top six ranked skaters.
"I am very grateful for my team and for the physician here," said Glenn, who suffered an ankle injury in Tuesday's practice session, after her victory.
"I've accomplished my goal, which was to be consistent throughout this Grand Prix, and I want to continue doing that at the Final."
In the men's, Mikhail Shaidorov of Kazakhstan landed a series of sensational quadruple jumps in a routine that earned him a personal best free skate score of 182.96.
But Japan's Shun Sato, who led the standings by five points after the short programme, scored 179.73 to hold off Shaidorov and claim the first Grand Prix victory of his career.
"I'm very satisfied with my performance today, despite a couple of mistakes," the 20-year-old Tokyo-based political science student said after winning with a total score of 278.48.
European champion Adam Siao Him Fa was third after battling through his Dune-inspired routine, putting a hand down and over-rotating during some of his jumps.
The French skater struggled with injury this season but has still qualified for Grenoble.
Italians Sara Conti and Niccolo Macii won the pairs event after an emotional free skate -- a tribute to Conti's late father performed to "Papa, Can You Hear Me?" -- proved enough to cling on to the top spot they occupied overnight.
"The tension was so high," Conti said after the pair's first Grand Prix victory was confirmed.
"It was not the perfect free programme, but we are so, so happy."
German pair Minerva Fabienne Hase and Nikita Volodin's huge free skate score of 140.92 wasn't enough to overhaul the Italians, who triumphed by less than two points. Lia Pereira and Trennt Michaud of Canada took third.
In the ice dance, Italian couple Charlene Guignard and Marco Fabbri bagged first with their robot-themed programme, ahead of Canada's Marjorie Lajoie and Zachary Lagha.
Both pairs qualified for Grenoble, at the expense of Christina Carreira and Anthony Ponomarenko of the US, who placed third in Chongqing and will therefore miss the final.
