The BORA-hansgrohe rider finished the 175-kilometer (108.7-mile) stage from Ecija to Sierra de La Pandera in 4 hours, 42 minutes, 10 seconds. But it didn't pay off as Froome got help from Sky teammates Mikel Nieve and Wout Poels to keep Nibali in sight - and then reeled the Italian back before beating him to the finish line.
Nibali, who did not compete in this year's Tour, waited his turn to attack while Alberto Contador, Romain Bardet (AG2R) and Lopez formed a group ahead of Froome's bunch.
Triple stage victor on the Tour de France, Majka had already picked the color last weekend, but he had failed in 3rd place at the 8th step. I had to win.
Nibali did gain four bonus seconds on Froome, but the Team Sky rider still heads the GC by 55 seconds from his Bahrain-Merida rival.
Froome had terrible memories of last year's Vuelta stage 15, when Alberto Contador and eventual victor Nairo Quintana attacked from the starting gun, leaving the Briton isolated from his team and wrecking his bid to win the overall race.
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Victory also moved Lopez up to sixth overall, ahead of Astana teammate and 2015 Vuelta victor Fabio Aru.
"I knew it was a risk, but I preferred to take it". "We have seen everything at this Vuelta. crashes, attacks".
Sunday is another gruelling mountain stage with a 129.4km ride from Alcalá la Real to Alto Hoya de la Mora, Sierra Nevada.
"At the end of a really hard week it's going to be one of the most decisive stages of this year's Vuelta", added Froome.
"Anything can happen", warned the Spanish (8th in 3 minutes and 19 seconds), at which it remains, "seven days of cycling in the legs" before retiring on the evening of the final stage, the 10 September in Madrid.