Knight and Szokol closed with a five-under 65 in better-ball play at Midland Country Club on Saturday.
They finished at 23 under, following a better-ball 61 in the second round on Thursday with an alternate-shot 62 on Saturday to take a three-stroke lead into the final round.
Finland's Castren and Tan, of Malaysia, carded a 63 to finish a shot back and repeat their second-place finish of last year.
The 26-year-old Knight also won the 2019 Ascendant LPGA, while for Szokol the win brings a first title on the Tour.
The US duo tied for fourth last year after missing the cut in 2021.
The teams of Celine Boutier (France)-Yuka Saso (Japan, 62), Jodi Ewart Shadoff (England)-Emma Talley (USA, 63) and Celine Borge (Norway)-Polly Mack (Germany, 63) tied for third at 20 under.
Australia's Sarah Kemp and her playing partner Alena Sharp, of Canada, carded an equal-best final-round 60 - 10 under for the day - to finish in eighth place at 16 under overall.
Karis Davidson, playing with Ecuador's Daniela Darquea, was three shots further back in joint 13th place after a last-day 62, while all-Australian pair Hannah Green and Su Oh finished tied for 26th at nine under.
12°C