Mueller chested down a long arcing pass from Yoshimar Yotun from beyond midfield, beat a defender and, from the top-right corner of the 6-yard box, shot and scored to open proceedings in the second minute.
Sacha Kljestan added a goal in the 35th and Dominic Dwyer scored in the 69th minute to give Orlando City a 3-0 lead. Mueller ran onto a long pass down the middle from Yotun and, as goalkeeper Andrew Tarbell charged, tapped it to Kljestan for the sliding empty-net finish from close range.
Justin Meram's through ball led Dwyer into the box where he sidestepped Tarbell near the spot and chipped it in to make it 3-0.
Florian Jungwirth scored in the 78th and 90th for San Jose, the visitors couldn't pull back a third goal. The Earthquakes are winless, including three losses, in their last five games.
Orlando City 3-2 San Jose: Lions hold off the Quakes - Via MLS
Forward Dom Dwyer scored his 100th professional career goal, as Orlando managed to fight off a late comeback from San Jose.