The 140-kilometre race blew apart on the biggest climb of the race with 21 kilometres remaining when Deignan attacked with teammate Elisa Longo Borghini and only Niewiadoma could follow. The trio held a small margin over the last kilometres and successfully fended off the chase to contest the win.
Deignan out-gunned Niewiadoma to the line after a lead-out from teammate Longo Borghini, who finished in third.
An emotional Deignan crossed the finish, winning the queen stage and also overtaking Niewiadoma for the race lead by one second with one stage remaining.
"The win felt very emotional," said Deignan. "It’s a comeback after becoming a mom; finding my feet again in cycling has been difficult.
"Obviously, there’s always been questions whether I made the right decision, but today was massive validation for that. My husband (former pro cyclist Phillip Deignan) has been my rock, and I thought of him when I crossed the line."
“I would not have believed you if you said I would be in the leader’s jersey after today. It’s just all coming together and racing with Elisa has been fun. I always knew we would be good teammates, we complement each other’s racing styles really well, and it has just been about me getting that race fitness back and then gelling with Elisa.”
The rest of the peloton had mounted a concerted chase to bring back the escaped trio, but could only get to within 16 seconds of Deignan's finish, with Leah Kirchmann (Team Sunweb) leading the chase over the line.
Australia's top finisher was Brodie Chapman (TIBCO-SVB) in 15th on the stage, with Rachel Neylan (Team Virtu) also finishing near the front of the race and moving up to 14th in the general classification.