The former world champion thrilled a huge crowd in Harrogate with a solo victory after pulling clear late in the race.
Deignan had also attacked last year, in the race from her home town of Otley, but was caught by the peloton before the finish in Doncaster.
This time there was no stopping the home favourite as she completed the 122.5km course in three hours, nine minutes and 36 seconds, 55 seconds ahead of runner-up Coryn Rivera, of Team Sunweb.
Wiggle High 5’s Giorgia Bronzini was third in the same time.
An emotional Deignan, of the Boels Dolmans team, said: “It was incredible.
“We knew we had to make it a tough race and it pretty much went to plan tactically. We sent Amy [Pieters] up the road in a breakaway and me and Anna [van der Breggen] jumped across to her and we knew from that point we had the race in our hands.
“The whole team was fantastic.”
Deignan was in an eight-strong group which broke away after the Cote de Lofthouse split the pack around 60km from the finish.
She, van der Breggen and Dani King moved ahead before the Yorkshirewoman made the decisive move with around 14kms remaining.
The 28-year-old revealed she went against orders late on.
“The chase group was coming pretty close and my director actually said wait for the sprint, you are coming back,” she reported..
“I thought I no I am not going to wait for the sprint. I know the roads better than you and it’s not coming back.”
The race captivated thousands of fans on the roadside and Deignan described the reception from spectators as “special and surreal”.
She added. “I can’t get my head around how many people came out to support us, it was really, really good.”