The Dane, who retained his Tour de France title this year, went off like a rocket on the steep finish to the 120km run through the Cantabrian valleys to outclass the peloton.
His American teammate Sepp Kuss struggled in the finale and lost more than a minute to Vingegaard but hangs on to the red jersey with a reduced buffer of 29 seconds.
Three-time Vuelta winner Primoz Roglic completes a Jumbo-Visma top three in the GC standings and is 1:33 behind Kuss. Spain's Juan Ayoso (UAE Team Emirates) is fourth, 2:33 adrift.
The Jumbo-Visma team were reeling earlier on Tuesday after the news that their rider Nathan van Hooydonck was in hospital after suffering serious injuries in a car accident at home in Belgium after falling ill at the wheel.
Vingegaard, who counted on teammate Van Hooydonck's steadfast support during his ride to the Tour victory this year, looked emotional after crossing the finish line.
"I'm just happy to win today because we had some terrible news this morning and I wanted to win for my best friend today," Vingegaard told Eurosport after his second-stage win at this year's Vuelta.
"Luckily now there is good news about his condition and it's a big relief for me and for the team."
After Monday's rest day, there was no gentle return to action and although the stage from Liencres Playa was classified as flat until the steep finish, it was anything but relaxing.
The pace was relentless over the rolling terrain with the peloton trailing behind an escape group that contained Kaden Groves (Alpecin-Deceuninck) who topped up his points total.
Jumbo-Visma's pace ensured the breakaway was eventually reeled in and then it was every man for himself on the 4.8km slog to the finish with gradients reaching 15%.
Any notion that Kuss might be shepherded into Bejes by Vingegaard and Roglic floundered as Vingegaard got out of his saddle and blasted up the slopes.
Finn Fisher-Black (UAE Team Emirates) tried to respond but finished second on the stage by 43 seconds with Wout Poels (Bahrain Victorious) six seconds further back.
Roglic seemed in two minds whether to try and close the gap on Vingegaard or stay with Kuss and finished just over one minute behind to slip a place in the GC standings.
Kuss was philosophical about being attacked by his own teammate on the final climb.
"I don't want to win this Vuelta as a gift, that is not sport. They know what I've done for them, but they're also winners," he said.
Wednesday's stage concludes at the infamous Angliru climb when Vingegaard will be the favourite to take the red jersey.
Jumbo-Visma are poised to become the first team to win all three Grand Tours in a single season after Roglic won this year's Giro d'Italia.
