Dominic Thiem needed a final-set tie-break to reach the semi-finals of the St. Petersburg Open at the expense of Daniil Medvedev and Stan Wawrinka saw off defending champion Damir Dzumhur. Klizan lost his first two match points but converted his third to reach his first final since the Austrian Open in July.
Making his first tournament appearance since winning the 2012 title, Klizan ended Wawrinka's quest for his first St. Petersburg crown.
Klizan had never beaten Wawrinka in three attempts, but the Slovakian came from a set down to win 4-6 6-3 7-5 on Saturday.
Thiem defeated fifth-seeded Roberto Bautista Agut of Spain 6-4, 6-3 in Saturday's other semifinal.
Thiem is 10-7 in career finals and 2-2 this season, most recently losing the Roland Garros final to Rafael Nadal.
Although Wawrinka, who seeks to regain top form after undergoing knee injury in 2017, created six break points he managed to convert only two, compared to Klizan's three service breaks out of four opportunities. "Stan is one of the best players in the world and I'm really proud of myself after I could beat him finally".
Elsewhere, top seed Kei Nishikori remains on course for his first title since 2016 after overcoming Nikoloz Basilashvili in three sets at the Moselle Open in Metz.
Matthias Bachinger will be Nishikori's semi-final opponent after he sent fellow German Yannick Maden packing.
He wasted the first when his forehand landed long and Stan repelled the second with a service victor, rattling one easy service game after another to stay in front all the time.