Federer improved to 12-0 head-to-head against the German thanks to a 6-4 6-2 7-5 fourth-round victory on Arthur Ashe Stadium on Monday.
However, the Swiss third seed did take a medical timeout off court at the end of the second set.
The 19-time grand slam champion was seemingly troubled by his back again, but he showed few signs of injury during a 109-minute win.
Into a 12th quarter-final in New York, Federer produced a fine performance against Kohlschreiber, setting up a clash against Del Potro in a repeat of the 2009 decider and moving a step closer to a last-four meeting with Rafael Nadal.
It continued a friendly run into the last eight for Federer, who has now beaten three players against whom he holds perfect records – Mikhail Youzhny (now 17-0), Feliciano Lopez (13-0) and Kohlschreiber (12-0).
Kohlschreiber matched it with Federer early, only to give up a 40-0 lead and be broken in the seventh game when the Swiss star hit a forehand winner.
That allowed Federer to take control, two more breaks – and losing just four points on serve – seeing him through the second set.
Unusually, the 36-year-old took a medical timeout before the third set, but he broke in the 11th game thanks to a backhand winner on his way to a straightforward victory.
STATISTICAL BREAKDOWNFederer [3] bt Kohlschreiber [33] 6-4 6-2 7-5
WINNERS/UNFORCED ERRORSFederer - 39/20Kohlschreiber - 19/33
ACES/DOUBLE FAULTSFederer - 11/2Kohlschreiber - 4/2
BREAK POINTS WONFederer - 4/7Kohlschreiber - 0/0
FIRST SERVE PERCENTAGEFederer - 65Kohlschreiber - 57
PERCENTAGE OF POINTS WON ON FIRST/SECOND SERVEFederer - 88/73Kohlschreiber - 67/49
TOTAL POINTSFederer - 101Kohlschreiber - 70
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