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The American super-domestique dropped his breakaway companions in the final three kilometres of the climb to the Observatorio Astrofisico de Javalambre for a spectacular victory, 26 seconds ahead of Lenny Martinez (Groupama-FDJ) and 31 seconds ahead of Romain Bardet (Team DSM).
Despite finishing second on the day, Martinez was able to ride into the red jersey to become the youngest ever overall leader of the race at 20 years old, Belgian superstar Remco Evenepoel (Soudal QuickStep) relinquishing the lead after a day of struggle.
As well as losing the overall lead, Evenepoel also lost 32 seconds to Jumbo-Visma duo Primoz Roglic and Jonas Vingegaard after they attacked on the final climb, though he retains a slim advantage on the pair in the general classification (GC).
“It was an incredibly hard stage,” Kuss said after the finish. “We wanted to try and go in the breakaway – just to test QuickStep.
“For the whole day, I felt super, super good. I was only thinking about when to go, when to try and make the difference. For the whole climb, I was just enjoying the environment that we have in the Vuelta. It’s always a special race for me.”
Previewed as a stage for GC fireworks, the day lived up to its billing with a 42-man breakaway eventually going clear after 70 kilometres of the 183.5 kilometre course containing 11 of the top 25 riders in the overall rankings.
Lenny Martinez (Groupama-FDJ), Marc Soler (UAE Team Emirates), Sepp Kuss (Jumbo-Visma), Steff Cras (Total Energies), Wout Poels (Bahrain Victorious), Jefferson Cepeda (Caja Rural-Seguros RGA), David De La Cruz (Astana Qazaqstan), Rémy Rochas (Cofidis), Juanpe Lopez (Lidl-Trek), Mikel Landa (Bahrain Victorious), Hugh Carthy (EF Education-EasyPost) and Attila Valter (Jumbo-Visma) all went off the front with current champion Remco Evenepoel (Soudal QuickStep) and Jumbo-Visma heavyweights Jonas Vingegaard and Primoz Roglic trailing in the peloton.
Extending their lead by as much as seven minutes at one point, the peloton brought the break's advantage down gradually, the gap still at almost four minutes by the time the race reached the base of the final climb, the Pico del Buitre.
Australian Michael Storer (Groupama-FDJ) came to the fore of the break to set the pace for teammate Martinez, steadily reducing the group, before Einer Rubio (Movistar) made the first big move with an attack four kilometres from the finish.
Only Romain Bardet (Team DSM) and Martinez could follow initially, before Kuss caught and dropped the trio inside the last three kilometres, pacing his own effort from there to seal a spectacular win by 26 seconds over Martinez and 31 seconds over Bardet.
Roglic was the most aggressive of the pre-race favourites for the red jersey, attacking clear of the peloton and having teammates Jonas Vingegaard bridge up to him, the pair the strongest as other contenders yo-yoed around them, with Enric Mas (Movistar) initially holding on before dropping, and Juan Ayuso (UAE Team Emirates) coming with a late surge after initially being slow to follow.
After a frenetic stage, the overall standings now paint a completely different picture to yesterday, Martinez leading by eight seconds on Kuss in second, and Marc Soler (UAE Team Emirates) moving up to third at 51 seconds off top spot.
La Vuelta a Espana continues tonight with a flat Stage 7 that puts the focus back on the sprinters. Watch from 10.55pm AEST on SBS VICELAND and SBS On Demand.