Deignan had been on the attack late in the 132km stage from Barnsley but finished in the main pack as Parkhotel Valkenburg's Wiebes out-sprinted Christine Majerus of Boels-Dolmans and Team Tibco's Alison Jackson.
Former world champion Deignan, who won the 2017 edition of this race, only returned to racing last month following the birth of daughter Orla in September.
The Trek-Segafredo rider took to the line in Barnsley in optimistic mood after finishing seventh in Liege-Bastogne-Liege last week, but found the legs were not there for her on Friday.
"Actually I struggled today," the Otley-born rider said. "I felt better in Liege last week. Hopefully tomorrow I'll come round. At the moment for me it's all about getting those races in getting my race rhythm.
"The head (is still there), definitely. I'm still so eager to get going and I'm finding it boring I can't attack like I used to. But that will come back a couple of races down the line."
It was a third win of the season for the impressive Wiebes, who won in a bunch sprint after a six-strong breakaway had been caught just a couple of kilometres from Bedale.
"It's one of the best wins of my career," said the 20-year-old.
"When the breakaway was caught I thought 'I can win this', and the team did an amazing job to put me in a strong position in the train.
"I looked back and saw I was going to win."
Many of the riders were keen to use the race to get a first-hand look at the Harrogate circuit which will form the finish of September's world championships, and it proved a valuable recce.
"I've been doing it wrong in training so I'm glad I actually saw the proper course," Deignan said.
"Just the final couple of corners, I come at it from a different angle. God knows how. The main points I've been doing properly. It's a good circuit, I like it."
