The tall 20-year-old showed no nerves in her first WTA final and her dominance and aggression reduced her experienced opponent to tears of frustrations in the second set.
It was the second day in a row that a qualifier had won her first WTA title at an Australian Open warm-up tournament after Bulgarian Tsvetana Pironkova won the Sydney International women's title.
"I can't explain in words how happy I feel," Muguruza said after receiving her trophy. "Last year I was injured for six months and it's amazing to be here.
"I won my first doubles title in Hobart last year so I guess I'm in love with Hobart now."
Muguruza failed to drop a set over the entire week and her first round opponent at Melbourne Park, 24th seed Kaia Kanepi, will have her work cut out on Saturday's evidence.
The world number 58 clambered all over Zakopalova's service, reducing the Czech to a 33 percent and 41 percent success rate on her first and second serves.
It was appropriate then that, having burst into tears at the final handover and fending off one match point, the 31-year-old should concede the match with her third double fault.
Later on Saturday, world number five Juan Martin Del Potro meets Australian defending champion Bernard Tomic in the Sydney International men's final.