Open by big-serving South African Kevin Anderson, who reached his first grand slam quarter-final with a 7-6(5) 6-3 6-7(2) 7-6(0) win on Monday.
Murray had battled his way back from two sets down in the second round against France’s Adrian Mannarino, but could not work another miracle against the 14th-ranked, 29-year-old Anderson, who swept the final tiebreak 7-0.
Anderson, the 15th seed who had lost the seven previous times he had reached the Round of 16 in a grand slam, broke through with a brilliant display of serving in the final tiebreak.
He cracked his 25th ace along with two other service winners in ending the match, the longest of the tournament, after four hours and 18 minutes.
The upset victory lifted Anderson into a last eight meeting against fifth-seeded French Open champion Stan Wawrinka of Switzerland, a 6-4 1-6 6-3 6-4 winner against American Donald Young.