"To go here, and play and win for the first time, it’s great," Muguruza said. "So I feel now more calm, more in the tournament."
Muguruza lost to Safarova in the French Open quarterfinals, the only other time they have met.
"I remember the last match I played against her," Muguruza said. "It was tough for me because I lost. I really wanted to go out on the court and try to win today."
Muguruza reached her first Grand Slam final this year at Wimbledon, losing to Serena Williams in straight sets. She was the first Spanish woman to reach a Grand Slam final since Conchita Martinez lost the French Open final in 2000, and the first to do so at Wimbledon since Sanchez-Vicario in 1995 and 1996.
Sixth-seed Angelique Kerber defeated fourth-seeded Petra Kvitova 6-2, 7-6 (3) for her second win in seven matches at the season-ending tournament.
It is Kerber’s third WTA Finals appearance but the German has yet to progress beyond the round-robin stage of the competition.
Kerber raced through the first set, but looked to be in trouble in the second as Kvitova was twice up a service break, but the Czech player couldn’t hold onto the advantage.
Kerber was broken when serving for the match at 5-4, but managed to secure victory in the tiebreaker.