The Czech and American duo beat their second-seeded Kazakh and Serb opponents 6-2, 7-5 in just over 90 minutes on Court Philippe Chatrier.
For Siniakova and Townsend, it was a third major title as a pairing, adding to their wins at Wimbledon two years ago and at the 2025 Australian Open.
"I'm very proud of both of us. I mean, we have both fought through a lot over these past couple of weeks. I was sick first, then Kat, and just conditions, changes from hot to cold," Townsend said.
"So we've worked really hard to be able to hold this trophy."
Danilina and Krunic tasted defeat for the third time in as many Grand Slam finals.