Visma-Lease a Bike's Van Aert and Valentin Paret-Peintre attacked from a breakaway late in the 192.8km 13th stage from Almunecar to Loja.
The 31-year-old Van Aert was too strong for the Frenchman in a sprint for the line, clinching the fourth Vuelta stage win of his career after three victories in 2024.
"I had (the attack) a little bit in my mind, yes," said Van Aert. "I saw the profile, and I knew there was this last kicker before coming into the village."
"This distance a lot of the time is the moment when people start to think about the sprint, and if you're able to open up a gap, then they don't want to close it for each other anymore."
Britain's Matthew Brennan, who has won three stages already on the race, won the battle for third, 24 seconds behind the leading duo.
Mas, who has led the race since title favourite Tadej Pogacar crashed out during stage eight, kept his 01:45 overall lead ahead of four-time champion Primoz Roglic after finishing safely in the pack.
Austrian Felix Gall is 21 seconds further back in the final podium position, with former Giro d'Italia winner Richard Carapaz 03:53 off Mas's lead in fourth.
"It's tough, but we're in Andalusia, it's summer, with the heat," Mas said, before suggesting the idea of holding a riders' meeting about safety concerns if the heat continues to rise.
"We'll definitely feel the effects of today's heat tomorrow."
Van Aert was part of a large breakaway group early on a day marked by intense heat in southern Spain.
A smaller group of 10 riders later pulled clear and consolidated their advantage on a descent from the day's final climb with 37km left.
Van Aert attacked with 3.5km remaining and only Paret-Peintre managed to stay with him, until the last 100 metres.
Van Aert, who beat Pogacar at Paris-Roubaix earlier this year, also holds a commanding lead in the points classification.
The peloton face another tough day in the mountains in Saturday's 14th stage, a 154.5km ride from Jaen to La Pandera featuring two category-two climbs and a category-one summit finish.