Isner fired 18 aces, saved both break points he faced and broke Lacko three times on the way to victory, his fourth in four career meetings with Lacko.
The 20-year-old, who stunned Roger Federer en route to the Australian Open semi-finals last month, had lost his last two matches to Gael Monfils and Damir Dzumhur.
The Costa Mujeres center is an extension of Nadal's original academy based on his native Mallorca.
Naomi Osaka remains top of the standings, while Serena Williams returned to the top 10 for the first time since July 2017.
The three-time Grand Slam champion is on the road back to his best after serious knee injuries.
Monfils, the runner-up three years ago, held off Wawrinka's second-set surge to ease through the decider.
Track and field's global governing body wants to introduce the rule changes in order to promote what it says will be fairer competition between all female athletes.
Schnur, a 23-year-old from Montreal ranked 154th in the world, defeated 10-time ATP title-winner Querrey in one hour and 54 minutes in the semi-finals.
Switzerland's 2015 champion needed almost two and a quarter hours to defeat the Japanese star who was playing at the Dutch event for the first time.
The unseeded Belgian beat former champion Simona Halep in three sets.
The French showman left it late but gave the Ahoy Arena crowd a thrill as he broke in the penultimate game of the third set and served out the win a game later.
American Isner will now face compatriot Reilly Opelka, who defeated Spain's Guillermo Garcia-Lopez.
Tsonga, ranked a lowly 140 after 2018 knee surgery, had been on a roll in the Dutch port city, following his title victory last week in Montpellier.
Top-seed Halep to meet Elise Mertens in the final after the world number 21 beat Angelique Kerber.
Roger Federer, Novak Djokovic and Andy Murray will be missing the controversially rebooted tournament.