The Team Sky rider completed the 40.2-km run from Circuito de Navarra to Logrono in 47 minutes, adding 57 seconds to his lead over his main rival, Vincenzo Nibali (Bahrain-Merida), who is now 1min 58sec in arrears.
Froome finished 29 seconds ahead of the day's second-placed rider, Sunweb's Wilco Kelderman.
Kelderman's reward for a fine performance was to move onto the podium in the overall classification, behind Froome and Nibali.
This display recalled Froome's sensational performance in the 2011 time trial at the Vuelta, where he stunned team leader Bradley Wiggins by taking the red jersey in Salamanca.
"I wasn't getting many time checks from the car so didn't really know where I was," Froome said. "I actually thought it wasn't good news so I was worried halfway through.
"But coming into the last six or seven kilometres I found out I was on track for the stage, which was a big relief."
Team Sky general manager Dave Brailsford doesn't believe Froome has victory wrapped up yet, though, despite his convincing lead.
"It's so hard, the climbs are so steep and intense that you can never relax," he said. "We can tick that one off, turn the page and get back into the steep hills."
Daniel Oss (BMC) had set the early running but Lennard Kaemna (Sunweb) beat his time before being usurped by Tobias Ludvigsson (FDJ), who crossed the line in 48min 7sec.
Veteran rider Alberto Contador (Trek-Segafredo), in the final time trial of his career, set a new lead time of 47min 59sec, delighting his fans at Logrono and moving to fifth in the overall rankings, before Froome's resounding victory.
