The world No 5 missed the entire stretch of the European clay court season, including the French Open, due to injury and only returned to the tour for the first time in two months last week for the start of the grass court season.
Pegula, ranked No 5, will play her countrywoman and doubles partner Coco Gauff, the top seed, next. She holds a 3-1 lead over Gauff but the top seed has won their only meeting on grass which came at Eastbourne one year ago.
This will be Pegula’s first career grass court semi-final on the WTA Tour.
In the previous round of the tournament, the American beat Croat wildcard Donna Vekic (6-4, 7-5).
Siniakova, ranked No 30, won against American Emma Navarro (6-4, 6-3) and Chinese Qinwen Zheng, the No 6 seed (6-4, 6-4) earlier in the week.
Berlin WTA 500, other last eight results (Rot-Weiss Tennis Club, grass, USD 922,573):
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