The 37-year-old was taking on Kazakhstan's Alexander Bublik and trailed 2-1 in the opening set when he decided he would be unable to complete the match.
Bublik had broken serve and led 40-30 in the fourth game when Wawrinka approached the net and told the umpire he had to stop.
Wawrinka has been battling a thigh injury that appeared to be the cause of his withdrawal, meaning the three-time grand slam champion, now ranked a lowly 284th, could not push on with his quest for a first ATP Tour title in five years. His most recent semi-final appearance, prior to this run in Metz, had come in Doha at the start of 2020.
Italy's Lorenzo Sonego awaits Bublik in Monday's (AEST) final after he sank the hopes of No.2 seed Hubert Hurkacz in the first semi-final.
Unseeded Sonego took the win 7-6 (7-5) 6-4 and will be chasing a third ATP title, after previous triumphs in Antalya in 2019 and Cagliari last year.
Bublik, the No.7 seed this week, has just one previous singles title, earning that success in February of this year in Montpellier.