The two-time champion has not lost at the Stadthalle since the 2008 quarter-finals against Spaniard Feliciano Lopez and next faces South African Kevin Anderson for a spot in the semi-finals.
Melzer fired seven aces in his 83-minute win against the six double-faults of Garcia-Lopez, breaking in the final game of the first set and running away with the second.
German veteran Tommy Haas, a qualifier, also made the quarter-finals as he beat Slovenian 204th-ranked unknown Aljaz Bedene 4-6, 6-4, 6-1.
Haas, 33, coming back from a 2010 hip surgery, won the Vienna title a decade ago and was runner-up the previous year. He is playing the tournament for the first time in five years, standing 19-7.
German Daniel Brands joined Haas in advancing as he upset Czech fourth seed Radek Stepanek 6-4, 7-6 (7/4).
There was an anti-climax for Austrian teenager Dominic Thiem as the youngster, who ended the career of former world number one and 1995 French Open champion Thomas Muster in the first round, lost to Belgian Steve Darcis 6-2, 6-2.
Xavier Malisse of Belgium defeated Italian eighth seed Fabio Fognini 6-7 (3/7), 6-3, 6-3.
Later Thursday, top seed Jo-Wilfried Tsonga was making his tournament debut when he faced last weekend's Stockholm finalist Jarkko Nieminen of Finland.
Jurgen Melzer keeps up perfect push
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