Two days after his 25th birthday, Lotto-Soudal rider Wellens was with a five-man breakaway before sprinting clear on the climb towards the finish line on top of the Aremogna.
It was the first Grand Tour stage victory of his career and followed team mate Andre Griepel's win on Wednesday.
For much of the 157 km stage, a three-man break of Alexandr Kolobnev, Alessandro Bisolti and Eugert Zhupa were out ahead, building up a lead of six minutes.
The gap was cut back to less than a minute on the descent of the categorised Bocca della Selva, about 75km from the finish, but there was no real urgency to reel them in as Wellens, team mate Pim Ligthart and Laurent Didier bridged to the leaders.
Didier made the first move on the final 9.25km climb towards the finish, but Wellens responded and quickly opened up a gap that he never looked like losing.
"It was ideal with Pim Ligthart attacking from the front," Wellens said. "We bridged to the front leaders, and the front leaders were already tired. On the last climb I was the strongest. I had a very good feeling."
Tom Dumoulin (Giant-Alpecin) attacked the peloton to stretch his overall lead to a useful 26 seconds ahead of Friday's 211 km stage from Sulmona to Foligno which features a flat last 40km that suits the sprinters.
(Reporting by Martyn Herman; Editing by Tony Jimenez and Pritha Sarkar)
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