In her first professional match in nearly half a year, world number two Halep, who skipped last week's Palermo Open and will not make a decision on whether to play the US Open or not until after the tournament in the Czech Republic, was made to work hard for victory by the unseeded Hercog.
With second-ranked Simona Halep joined by 2017 French Open champion Jeena Ostapenko and last years Roland Garros finalist Markta Vondrouov, this years Palermo Ladies Open, the August 3-9 event marking the return of tour-level tennis following a five-month break for the coronavirus pandemic, will be like no other. Before the Wimbledon champion recovered from a foot injury she sustained in Dubai, the coronavirus pandemic forced a five-month break.
Having secured a crucial break to move 5-3 ahead in the third set, Halep dropped her own serve before squandering three match points.
"I feel I'm playing better on clay each year, " Pliskova said. "The fighting helped me to win the match".
A number of other seeded players were not as successful.
No.2 seed Petra Martic of Croatia bounced opened her Prague Open campaign with a 7-6 (2), 6-3 victory over Russian Varvara Gracheva.
However, four of the top-10 seeded players went out.
Fifth-seeded Ekaterina Alexandrova was upset by Lesia Tsurenko 6-2, 6-4, sixth-seeded Anastasia Pavlyuchenkova was knocked out by Arantxa Rus 7-5, 6-2 and Irina-Camelia Begu dispatched ninth-seeded Anastasia Sevastova 6-2, 6-2.
Camila Giorgi, Magdalena Frech, Ana Bogdan and Leonie Kung also advanced.
The Prague Open is the second European tournament since the WTA restarted amid the coronavirus pandemic, with strict health protocols in place.