The Spaniard defeated the eighth seed 6-0, 6-4, and so will play Roger Federer in the semi-final on Saturday.
"I'm glad to beat Janko tonight," said del Potro. "I play much better than my first match here [against Ferrer]. [A] win in two sets gives me a chance to go to the next [match]. I know if I want to beat Roger, I should play much better than today and my first match."
Del Potro lost just five points on serve in the 28-minute first set, as an under-the-weather Tipsarevic won two of 13 points on his second serve and committed 11 unforced errors.
Tipsarevic got on the scoreboard after he won a 12-point and nine-minute opening game in the second set, saving one break point, much to the delight of the crowd at The O2 in London. After receiving two newly strung racquets, Tipsarevic’s competitive drive returned, but del Potro took opportunity to break to 30 for a 3-2 lead. It all but ended the Serbian’s resistance.
Del Potro is now 4-0 lifetime against Tipsarevic and improved to a 64-16 match record on the year, which includes four titles. He is also 7-13 in 2012 against Top 10 opponents. Tipsarevic, who was an alternate last year, is now 1-4 at the tournament and 57-27 this year.
Del Potro hit six aces and won 21 of 25 points on his first serve against Tipsarevic, who won 39 of 61 total points. The match, which was watched by 17,641 spectators, lasted 77 minutes.