However, having lost the first set, the 21-year-old produced two sets of the highest calibre of tennis to claim a first Grand Slam title, taking the second of the championship points on offer, courtesy of a double fault from Muguruza.
"This is my first speech but I’ll try my best,” Kenin said on court after the match.
My dream has officially come true, I can’t even describe this feeling. It’s so emotional and I worked so hard. I’m just so grateful to be standing here. Dreams come true. If you have a dream, go for it and it’s gonna come true.
Muguruza had arrived in Melbourne suffering from a virus that forced her to quit the Hobart International, but the Spaniard was soon back to playing to her strength which helped her reach the top of the women's rankings in 2017.
Some of the inconsistency that led to her slipping to 36th in the rankings last year resurfaced against Kenin, however, as the Spaniard blew hot and cold with her serve, getting 57% of her first serves in while mixing her nine aces with eight double faults, with the eighth double handing the title to Kenin.
Top 5 Shots from Kenin v Muguruza - Thunderous forehands, incredible defence & deft drop shots
Kenin came to the match with a game plan, mixing deft drop shots with her deep forehand groundstrokes to catch Muguruza by surprise initially.
But the Spaniard soon found her range and converted her third breakpoint in the third game to nose ahead in the opening set.
Kenin, who beat Ash Barty in the semi-final despite trailing the world number one for most of the match, refused to throw in the towel and boosted her confidence by saving four breakpoints to hold the seventh game.
She was rewarded for her tenacity in the next game with two consecutive double faults from Muguruza that gave the American a break back, and brought the set back on serve.
But the Spaniard came out firing on all cylinders to break the Moscow-born Kenin again and took the opening set when her opponent missed the sideline with her forehand.
Highlights: Kenin downs Muguruza to win Australian Open
Kenin took the court in the second set with renewed vigour as the power behind her shots went up a notch. She got the break in the fourth game and then a confident hold gave her a 4-1 lead.
There was no comeback for Muguruza from there as the American levelled the match with the second break of her serve.
The intensity of the deciding set rose considerably with Muguruza slapping her thigh to urge herself on while Kenin was almost reduced to tears out of frustration at some of her shots.
Down 0-40 in the fifth game and with her back to the wall, Kenin probably produced her best tennis. She painted the sidelines with three scorching winners while also producing an ace to hold serve for 3-2.
A fifth double fault from the Spaniard gave Kenin a 4-2 lead, and she was suddenly within striking distance of victory, which she sealed by breaking her opponent again as a nervous Muguruza served three double faults in the final game.
"I think I'm gonna keep it short because I'm going to get very emotional," said Muguruza, before congratulating her opponent. "I have to thank my team ... they were over there suffering with me today."