With his side seemingly in the helpless position of 4-59 chasing 156, De Villiers intervened spectacularly with a 41-ball innings featuring six fours and eight sixes.
Earlier, David Warner's 61 had underpinned a solid total of 6-155 after Hyderabad were asked to bat.
Their hopes were almost immediately undermined, Mitchell Starc (2-21) having Australia team-mate Aaron Finch caught behind on the hook for just 13.
Hopes of an immediate response were snuffed out, too, as Lokesh Rahul edged an attempted cut off Ashok Dinda (1-39) to slip.
Warner and Shikhar Dhawan responded well, sharing in a 62-run stand.
While Dhawan was more circumspect than usual, his 37 coming off 36 deliveries, Warner produced his muscular best.
The Australian, who began with a first-ball crunch through the covers, struck four fours and three powerful straight sixes in a 49-delivery stay.
He was eventually bowled by Starc in the final over, although not before seeing his side beyond 150.
Bangalore got off to a similarly poor start to their counterparts in the reply, Bhuvneshwar Kumar (2-16) beating the bat of Parthiv Patel first up with a delivery that swung back.
The seamer was not finished there, grabbing a key wicket when Virat Kohli feathered an attempted cut behind.
Karn Sharma then got in on the act, having Chris Gayle - who had struck a couple of typically lusty sixes en route to 27 – caught at deep midwicket before trapping Rilee Rossouw lbw.
De Villiers began to find his feet thereafter, a series of powerful sixes coming amid a flurry of fours as his 50 was brought up from 23 balls.
Yuvraj Singh fell just before that, sweeping Sharma to deep backward square-leg, yet de Villiers powered on.
Even so, 27 were required off the final two overs – the first of which was bowled by Dale Steyn.
But De Villiers got the better of his South Africa team-mate, crunching successive sixes to start the over before ending it with a lofted four and a scooped maximum.
Starc was run out at the beginning of the next over, but De Villiers struck the penultimate ball for four to seal a memorable win.