After Magnus Eriksson put the Earthquakes (13-10-5, 44 points) up 1-0 in the third minute, Wondolowski followed in the 20th and 33rd minutes to give him 13 goals for the season and 157 in his 354th career game.
Orlando City (9-13-7, 34 points) has two losses and a tie in the past three games.
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The Earthquakes ran their home unbeaten streak to 12 (10-0-2) as Daniel Vega made one save for his seventh shutout.
Unlike the previous match, when they fired a league-record 25 shots in the first half, the Earthquakes had 13 with seven on target.
Eriksson's sixth goal made it 1-0 by taking a pass from Jackson Yueill in stride, splitting two defenders with the dribble and nutmegging goalkeeper Brian Rowe, who had six saves.
Wondolowski in transition added to the lead. He stayed onside for the leading pass by Valeri Qazaishvili and chipped a shot into the far netting.
Cristian Espinoza earned his 12th assist this season for the 3-0 lead. He was denied by Rowe but got the ball back and sent a cutback service to Wondolowski in front for the finish from the middle of the box.
Wondolowski's 33 multi-goal games are 11 more than runner-ups Jeff Cunningham, Landon Donovan and Ante Razov in MLS history.
The victory was the first in four tries against Orlando City after three losses and a tie.
San Jose coach Matias Almeyda served the first of a two-game suspension after being ejected from the Aug. 23 match vs. Los Angeles FC for his on-field conduct. He will also miss the game against Real Salt Lake on Sept. 11.
Orlando City is home Sept. 7 to play league leader LAFC.
Earthquakes lead inside 5 minutes vs. Orlando
Major League Soccer: Magnus Eriksson (3') San Jose Earthquakes 1-0 Orlando City. To watch MLS, sign up to ESPN+.
Wondolowski, Earthquakes make easy work of Orlando City
Chris Wondolowski added two goals to his MLS career record as San Jose dealt Orlando City's playoff hopes a big blow. To watch MLS sign up to ESPN+.