The 23-year-old Wimbledon champion, who climbed to the top of the WTA rankings on Monday, hardly broke sweat against the Frenchwoman, ranked 20th in the world, on her way to victory in an hour and 20 minutes.
Muguruza took a 2-1 lead in the first set after an early break and continued to dominate until midway through the second, nullifying Garcia's serve twice more as she looked to close out the contest quickly.
Garcia, however, staged a mini-revival when she converted her only break-point opportunity in the sixth game of the second but the Spaniard regained control of the contest with another break in the very next game.
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The 2016 French Open winner will face either defending champion Caroline Wozniacki of Denmark or Slovakia's Dominika Cibulkova in the last four.
Earlier, Germany's Angelique Kerber won a battle of former world number ones against Karolina Pliskova 7-6(5) 7-5 to set up a semi-final clash against Anastasia Pavlyuchenkova.
The two-time grand slam champion, who defeated her Czech opponent in their last meeting at the 2016 U.S. Open final, converted her fifth match point to register a first win over a top-20 player this season.
"Being back in the semis here in Tokyo is a great feeling," said Kerber, who last reached the semi-finals at the event in 2014, in a courtside interview.
"It's always tough to play against (Pliskova), so I was trying to focus on my game. I think I played a good match today."
Nimble on her feet, Kerber, who has dropped to world number 14 since storming to the Australian and US Open titles last year, put immense pressure on Pliskova's serve but failed to convert 12 of her 13 break-point opportunities.
She did, however, hold her nerve during the first set tie-break to edge ahead and then finally broke in the 12th game of the second set to seal a spot in the last four.
Russian Pavlyuchenkova defeated another Czech player, Barbora Strycova, 5-7 6-3 6-1 to advance to the semi-finals.
PAN PACIFIC OPEN WOMEN'S SINGLES QUARTER-FINALS RESULTS
1-Garbine Muguruza Blanco (Spain) beat 9-Caroline Garcia (France) 6-2 6-4
7-Angelique Kerber (Germany) beat 2-Karolina Pliskova (Czech Republic) 7-6(5) 7-5
Anastasia Pavlyuchenkova (Russia) beat Barbora Strycova (Czech Republic) 5-7 6-3 6-1
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