Argentina's Del Potro, who lost in last year's finale to Jo-Wilfried Tsonga of France, fired 30 aces in his marathon 6-7 (5-7), 7-6 (7-4), 7-6 (8-6) win over German qualifier Daniel Brands.
Brands served up 32 aces of his own in the 3-hour, 5-minute struggle at Wiener Stadthalle.
Meanwhile, Austrian crowd favorite and two-time champion Jurgen Melzer wasn't as successful -- the No. 4 seed succumbed to Luxembourg's Gilles Muller 6-3, 3-6, 7-6 (7-4).
American Donald Young surprised fifth-seeded Italian Fabio Fognini 7-6 (10-8), 6-3 in first-round action Wednesday, while Austrian wild card Dominic Thiem bested Poland's Lukas Lacko 7-6 (7-3), 6-3.
Celebrity Breakups and divorces of 2014 [PHOTOS]