The Czech seventh seed played some brilliant tennis to edge Murray in a marathon first set but was on the back foot thereafter to lose 6-7 (6) 6-0 6-3 7-5 on a chilly night at Rod Laver Arena.
"I'm really not happy and not really in a good mood," a downcast Berdych told reporters.
"I'm very disappointed to lose this match. It was a big match. I just need to come back stronger.
"What was the difference? I had one bad set for the second set and that's it. I was just trying to get my chances, trying to fight for it, but it was not enough."
The big-serving Czech thrashed third seed Rafa Nadal in straight sets in the previous round, ending a 17-match losing streak to the Spaniard.
Much has been made of coach Dani Vallverdu's part in Berdych's run in Melbourne, having joined the Czech after leaving Murray's camp.
Berdych credited Vallverdu for helping him devise a master plan for Nadal but the respected Venezuelan was unable to make the difference against the sixth seed.
The glaring streetfighter that punched hard in the opening set was replaced by a lumbering giant in subsequent sets as Berdych was thrown by the Scot's superior court speed.
Murray appeared fired up after an exchange between the first and second sets but his opponent said he was misunderstood.
"I say to myself, 'Well done, Tomas'." Berdych said. "I think I'm allowed to do that when I win a set. That was it.
"There is no really big deal about anything that was happening today on the court.
"It was a great battle, a good match. Unfortunately with a bad end for me. That's how it is. That's the sport."
(Editing by Tony Jimenez)
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