The world No.1 could not find rhythm on her usually dominant serve, winning just 55 per cent of first serve points and a mere 27 per cent on the second delivery in the 6-2, 6-2 defeat, throwing the top quarter of the women’s draw wide open and marking the first time in the Open Era the top two seeds in the women's singles have not reached the third round of a Grand Slam event.
It is the first time Williams has bombed out in the second round of a Grand Slam since losing to sister Venus at the Australian Open 16 years ago. The four games she managed to salvage were the fewest she had won in a major in 288 matches.
Murguruza, who first turned heads back in January where she won in Hobart as a qualifier before reaching the fourth round of the Australian Open, cracked 12 winners to eight off the racket of Williams and committed just 18 unforced errors to her opponent’s 29.
The 20-year-old - whose father is Spanish and mother Venezuelan - is still deciding which country to represent, but at the moment it matters little. For now, she will savour the biggest win of her career having defeated a player she grew up idolising.
"Of course it's a dream, you know. Since I was a child, I thought, 'Oh, I want to play against Serena on centre court', and today was the day, and I think I did very good," a beaming Muguruza said.
"I knew the match was going to go fast, because she plays really fast and I play really fast. I was thinking that ... if I change the way I was playing, then she will begin to feel better, you know, and turn around the match. But I said, 'OK, this is my chance. I'm going to continue doing the same no matter what happened'."
In what was tipped to be an all-Williams third-round affair, Muguruza will now face Slovak Anna Schmiedlova after the world No.56 earlier upset big sister Venus on Philippe Chatrier Court.
"Today you go to the court thinking, 'OK, I have nothing to lose, I'm playing against No.1 in the world'. You don't have expectations," Muguruza said. "But the next round is really the difficult one, because everybody is thinking, 'Oh, she just won a really good match. Now you have to win'. So the next match is really difficult, and I don't care who I'm playing."
Congratulating her opponent at net, Williams told Muguruza she would win Roland Garros if she continued to play the way she did on Wednesday. "That was a wonderful feeling. I'm so happy she said that to me. But I have to take it as a very fair play message of congratulations," Muguruza said.
When asked whether she was more popular in Spain or Venezuela and whether it allowed her to queue jump into nightclubs, the humble 20-year-old made it clear where she stood. "I'm not popular, not at all. But, I prefer like this," she grinned.
She could well be underestimating herself after this victory.
For all updates on the 2014 French Open visit www.rolandgarros.com.