The Russian, also 20, continued her sparkling run of form earlier in the evening when she outlasted American veteran Venus Williams in a three-set slugfest lasting almost three hours.
Osaka's defeat of the top-seeded Halep stood out as the bigger of the two upsets, which played out under the lights on a chilly night in the California desert city of Indian Wells.
The Romanian had won all three of her previous meetings with the emerging Japanese player and looked poised to make a run to reclaim the title she won in 2015, but instead put in a puzzling performance full of uncharacteristic errors and little fight.
WTA Indian Wells
Superb Osaka crushes Kasatkina in Indian Wells to win maiden WTA title
18/03/2018 AT 19:32
The match started as a cagey affair until it reached 3-3 in the opening set before Halep's game unravelled as she coughed up a litany of errors, paving the way for Osaka to reel off the next nine games without much resistance.
"It wasn't easy," Osaka said in a courtside interview. "I was really stressed out the entire time but I am really happy I could end it fast."
Halep offered few excuses for her baffling display but felt that the long wait to get on court had not helped her cause.
"I just didn't feel the ball at all. I was out of the game today. I played okay until 4-3 but then I just went out. I don't know why. I just lost my concentration," she said.
"She was better. She was more prepared and she was ready to play and ready to win the match. I was not."
While Osaka barely broke a sweat in her 64 minute victory, it was a different story for Kasatkina, who emerged the victor after a marathon 4-6 6-4 7-5 battle against Williams.
Kasatkina took advantage of a sub-par serving night from the more powerful Williams as the match progressed, forcing long rallies that ultimately wore her 37-year-old opponent down over the course of the contest.
The Russian, who fought back after being two points away from losing in the contest in the third set, dropped her racquet and put her hands on her head in shock after Williams sent a backhand into the net on match point.
"I'm a bit tired," Kasatkina said after the two hour and 50 minute encounter. "One more to go."
The win extends the Cinderella run for the tournament's 20th seed, who defeated grand slam champions Sloane Stephens, Caroline Wozniacki and Angelique Kerber without dropping a set before going the distance to take down Williams.
Williams played an excellent all-around game, mixing bruising ground strokes with frequent approaches to the net and moving well around the court.
However, she was unable to rely on her big serve at key moments and ended up getting broken seven times.
Kasatkina will have Saturday to recover before facing Osaka for the first time in their fledgling careers on Sunday.
Neither Kasatkina nor Osaka have much experience in big matches with the Japanese player's only career final coming in Tokyo in 2016 and her opponent's lone singles title coming in Charleston last year.

Results: WTA Indian Wells

WTA Indian Wells
Halep reaches last four, Osaka stuns Pliskova
15/03/2018 AT 00:28
WTA Indian Wells
Wozniacki loses, Halep, Kerber and Venus advance
13/03/2018 AT 20:46