Wondolowski, 36, is now on 148 goals in 338 MLS appearances, while Donovan took 340 games to reach the previous record of 145.
- Carlisle:How Wondo broke MLS' all-time goals record
His record-tying goal came in the 21st minute when Cristian Espinoza delivered a long, cross-field pass to Shea Salinas on the left wing, and Salinas' low, driven cross was stabbed home by Wondolowski at the far post.
Wondolowski set the new mark on 48 minutes when a seemingly innocuous cross from Nick Lima was floated into the box, but when Fire goalkeeper David Ousted fumbled the delivery, Wondolowski was there to pounce and side-foot it in.
He added additional strikes in the 74th and 76th minutes to round out his historic afternoon.
Wondolowski was later substituted to a standing ovation in the first minute of stoppage time as a congratulatory message from Donovan was shown on the video board.
"It's crazy," Wondolowski said of his record-breaking goal. "I love visualization, I always pictured hitting a 30-yard blast into the upper 90. I didn't really picture the goalkeeper dropping it and tapping it in."
He added: "It is rejuvenating and reignited this passion. I always wanted to do it and be done with it. I didn't picture a day like this. Getting so much joy right now. The locker room: the love and the respect."
Wondolowski waited 13 matches to tie and then break Donovan's record on Saturday, with his most recent MLS goal coming all the way back on Oct. 6.
"It is a relief now. I'm not going to lie," he said. "But it is still so surreal that I get a message from Landon Donovan -- that he even knows my name still is crazy and boggles my mind"
Earthquakes boss Matias Almeyda said he was "very happy" for his striker.
"We were just telling him that when I watch my videos, they are six or seven minutes long because I scored maybe seven or eight goals in my career," Almeyda said. "When Wondo is my age, he'll be able to sit down for an hour and a half to watch his goals.
"I just told him to enjoy this moment, and that's why I subbed him off when there was a little bit of time left. I saw his family, I saw his daughters, and, really,it's moving. I congratulate him and I'm happy to be part of his achievement from the outside."
Almeyda said he had a feeling Saturday might be a big day for Wondolowski.
"I can't say because it's going to seem odd to you guys. I was speaking to my interpreter and one of the staff, and I said, 'Maybe he'll score four goals today.'"
Wondolowski started his career with the Earthquakes in 2005, but he scored his first four goals for the Houston Dynamo, where he played from 2006 to 2009 after the franchise relocated.
MLS returned to San Jose in the 2009 season -- and so did Wondolowski, who had his breakout year in 2010, scoring 18 times in 28 appearances.
He had a record-tying year in 2012 when he scored 27 times to match Roy Lassiter's 1996 mark for most goals in a season. That mark was equaled by the New York Red Bulls' Bradley-Wright Phillips in 2014 before Atlanta's Josef Martinez surpassed the trio's mark in 2018.
Wondolowski also has 11 goals and 35 caps for the United States and was part of the squad that went to Brazil for the 2014 World Cup.
Rounding out the top five leading scorers in MLS history after Wondolowski and Donovan are Jeff Cunningham with 134 goals, Jaime Moreno (133) and Ante Razov (114).
ESPN FC U.S. correspondent Jeff Carlisle contributed to this report.
Wondolowski breaks Donovan's MLS goals record in San Jose rout
San Jose's Chris Wondolowski has broken Landon Donovan's all-time MLS goals record with the first two of four strikes in a 4-1 win over the Chicago Fire.
Wondolowski breaks MLS all-time scoring record
Major League Soccer: Chris Wondolowski (48') San Jose 2-0 Chicago Fire
Wondolowski ties MLS all-time scoring record with 145th goal
Major League Soccer (Chris Wondolowski (21') San Jose 1-0 Chicago Fire