The Monaco player recovered from a break down in all three sets to overcome the ninth-ranked Fils in a gruelling two-hour, 20-minute quarter-final at Ariake Colosseum on Sunday.
Vacherot fights back again
Fils made the stronger start and established an early advantage in the opening set, but Vacherot refused to panic.
The 18th-ranked player saved a set point while trailing 5-3 before turning the momentum around. He won four consecutive games to take the first set 7-5.
Fils responded in the second set, recovering from another early setback to level the match at one set apiece with a 6-4 victory.
Frenchman unable to close out deciding set
Fils again appeared in control of the deciding set after breaking Vacherot to move 4-2 ahead.
However, the Monégasque produced another stunning turnaround, winning the final four games of the match to complete a 7-5, 4-6, 6-4 victory.
Vacherot converted four of his nine break-point opportunities, while Fils managed three breaks from eight chances. Vacherot also struck 14 aces compared with six from his opponent.
The victory continues an impressive week for Vacherot, who had already defeated Alexander Blockx and Stefanos Tsitsipas on his way to the last eight.
Vacherot reaches another Tokyo semi-final
The win sends Vacherot into the semi-finals of the ATP 500 tournament, where he will face either Jiri Lehecka or Daniel Vallejo.
It also avenges his defeat by Fils earlier this year in Miami, where the Frenchman won their previous meeting.
Vacherot now moves into the final four having demonstrated impressive resilience throughout the Tokyo tournament, particularly when matches have appeared to be slipping away from him.
Fils' title defence ends
Fils entered the tournament as the defending champion and had been enjoying an impressive run in Tokyo.
The Frenchman, who was ranked ninth in the world entering the match, had defeated second seed Frances Tiafoe 6-3, 7-5 in the previous round after coming through qualifying.
His defeat means he will not be able to defend the title he won at the Japan Open in 2024.
Meanwhile, Vacherot's victory adds another major result to a season in which he has established himself as one of the notable rising forces on the ATP Tour.
Alcaraz also reaches semi-finals
Elsewhere in Tokyo, defending champion Carlos Alcaraz advanced to the semi-finals after Denis Shapovalov retired while trailing 7-6(3), 2-1 because of an upper right thigh injury.
Alcaraz will face fellow Spaniard Jaume Munar in the last four.
The Japan Open is being staged at Ariake Colosseum from 28 September to 6 October, with the tournament forming part of the ATP 500 calendar.