A half-million of the plates have been sold since they debuted in 2000, putting the East Lansing school squarely ahead of its rival to the southeast.
The University of Michigan in Ann Arbor's license plate has drawn about 362,000 patrons, third place behind a patriotic plate that debuted after the Sept. 11 terror attacks.
Michigan State officials say the popularity of their plate likely stems from the school's large alumni base in Michigan.
"We pride ourselves on being the university for the state, so it's definitely refreshing to hear we have the most popular one," MSU spokesman Jason Cody said. "Anytime you can get the Spartan brand more visible, it's a good thing."
The secretary of state's office for more than a dozen years has offered specialty license plates that help raise funds for the state's 15 public universities as well as a number of causes and nonprofit organizations.
The plate costs drivers $35 in addition to normal registration fees. Of that, $25 goes to the organization and $10 goes back to the state as a service fee to make the plate.
Renewing the tags for the plates costs drivers $10 extra. That goes entirely to the benefiting organization, said Fred Woodhams, spokesman for the secretary of state.
Michigan State has earned $6.2 million from the proceeds of the plates. Cody said the money is divvied up this way: 45 percent goes to athletics programs, 45 percent to student scholarships and the remaining 10 percent to auxiliary services.
In total, fundraising plates have generated more than $31 million in revenue for universities and causes.
Woodhams said fundraising license plates represent about 220,000 of the 8 million vehicle license plates in circulation, not including permanent trailer plates.