The 4-6 6-2 6-2 victory was only the second match the towering Argentine had played in 11 months since surgery to fix an issue with his left wrist and he felt the burn.
The defending champion, competing on a wildcard after his ranking slumped to 338, was given a code violation after taking too long at a change of ends.
"This is my second match on tour after one year. I need to breathe more than the other players," he told reporters.
Del Potro hit 11 aces against one double fault in a solid serving display but admitted his backhand, still shaky following the surgery, needed work.
"My game is to serve strong and try and make winners with my forehand," he said.
"If my backhand is okay, I will be aggressive with it in the future.
"But now I think I just need to hit the ball as well as I can and don't try to make winners with my backhand.
"I just need to play a lot of backhands during the point, and if I do that I will get confidence very soon to play aggressive as well.
He will face qualifier Mikhail Kukushkin in the quarter-finals after the Kazak overcame sixth seed Pablo Cuevas of Uruguay 7-5 7-5.
The ATP 250 event is one of the final tournaments before the Australian Open, the first grand slam of the year, gets underway on Monday.
In the women's tournament, Tsvetana Pironkova continued her winning run in Sydney to 14 matches after she reached the semi-finals with a 6-4 6-1 win over Barbora Zahlavova Strycova.
The Bulgarian world number 67 was a shock winner in Sydney last year after coming through three qualifying rounds to make the main draw.
She will now face Wimbledon champion Petra Kvitova who survived a two-hour epic duel with Australian wildcard Jarmila Gajdosova 4-6 6-3 6-4.
Elsewhere, no play was possible at the Hobart Invitational, where heavy rain washed out both day and night sessions at the women's event.
(Writing by Patrick Johnston in Singapore)
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