Urán beat both Quentin Pacher (Groupama-FDJ) and Jesus Herrada (Cofidis) in a tense sprint finish after overtaking the latter inside the final 200 metres.
It was the EF Education-EasyPost rider's first Grand Tour stage victory since 2017 and is the final piece in a set containing wins at the Tour de France and Giro d'Italia.
"It’s beautiful to win in the Vuelta. I’ve been looking for this for several years because I’d already won at the Tour and the Giro," Urán said after the race.
"I was against some quick riders, I had to preserve some energy to ride against people like (Marc) Soler. At 300m to go, I said 'I have to go now, it’s now or never'. This win shows that we always have to believe and fight."
The Colombian caught Herrada at the Monasterio de Tentudia - the summit finish to the 162.3-kilometre stage - but was earlier involved in the day's first proper escape alongside the likes of Marc Soler (UAE Team Emirates), Bob Jungels (AG2R Citroen) and Fred Wright (Bahrain Victorious).
Pacher, too, was among the breakaway and the 13-strong group worked well to distance themselves from the peloton before Lawson Craddock (BikeExchange-Jayco) made his move inside the final 20 kilometres.
Former EF teammate Urán, with Herrada, were the first to catch Craddock under the flamme rouge and were soon joined by Soler and Clément Champoussin (AG2R Citroen).
Herrada looked the favourite following his attack up the summit but quickly faded as the gradient increased, allowing Urán to take full control just in time ahead of second-placed Pacher.
Back in the peloton, Roglič's withdrawal - a result of his - meant overall leader Remco Evenepoel (Quick-Step Alpha Vinyl) had no qualms keeping his grip on the red jersey, with Enric Mas (Movistar) his closest challenger, 2'01" behind.
La Vuelta continues tonight with Stage 18 LIVE from 10:50pm (AEST) on SBS and SBS On Demand.
