The two former Qatar champions last met at the Australian Open in 2019, when Bautista Agut claimed a marathon five-set victory which, famously at the time, appeared as if it might signal the end of Murray's career.
But the former world No.1 Murray has been making a remarkable comeback and had appeared to be gaining in confidence in Doha during his first-round victory over Taro Daniel, who had beaten the Scot in the Australian Open.
But a couple of wild groundstrokes from the three-time grand slam winner in Wednesday's tie set the tone for a one-sided first set as the world No.16 Bautista Agut imposed his will.
He did not lose a point on Murray's opening service game and broke twice more to complete a first-set whitewash.
Murray finally held serve to make it 1-1 at the start of the second set but the Spaniard pinned Murray back behind the baseline with the depth of his shots to dominate the extended rallies.
The fourth game of the second set was to prove crucial, Bautista Agut taking advantage of a couple of loose forehands to recover a 40-0 deficit and then firing a volleyed winner after setting up a first break point.
The Scot's frustration grew in the final game as he smacked his racquet against the court after Bautista Agut delivered an ace to get back to 30-30 after being 0-30 down.
Another ace set up match point and Murray then missed a forehand wide to confirm one of the heaviest defeats of his career.
Alejandro Davidovich Fokina also claimed a 4-6 7-5 6-4 victory over Briton Dan Evans to set up an all-Spanish quarter-final with Bautista Agut.
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