Garrett Graham caught three touchdown passes for the Badgers (4-0, 1-0 Big Ten), who avenged a last-second loss to the Spartans last season.
Michigan State (1-3, 0-1) turned the ball over four times after committing two turnovers in three non-conference games. Wisconsin converted three of the turnovers, including two first-half interceptions, into touchdowns.
Tolzien was 19-of-31, hitting Graham for three scores and Nick Toon for another. Graham tied the Wisconsin record for TDs in a game by a tight end and set the career mark (13). He finished with five catches for 58 yards.
John Clay rushed for 142 yards and a touchdown for the Badgers.
Tolzien and Graham hooked up for two touchdowns in the first half as the Badgers built a 21-7 lead.
After the teams traded field goals to start the second half, Cousins hit B.J. Cunningham for a 20-yard scoring pass late in the third quarter to pull the Spartans within 24-17.
But the Badgers wrested the momentum back immediately, as David Gilreath returned the kickoff 32 yards and Tolzien found Isaac Anderson on a sideline route for 45 yards on the first play of the drive. Three plays later, Tolzien hit a streaking Nick Toon for a 19-yard score on the first snap of the fourth quarter.
After a Michigan State fumble, Tolzien found a wide-open Graham for a 23-yard score and a 38-17 lead.