Russell Wilson threw for 345 yards and three ranked Wisconsin Badgers dominated the South Dakota 10.
Wilson completed 19-of-25 passes for the Badgers (4-0), who are off to a 4-0 start for a third straight year.
Nick Toon had a career day with seven catches for 155 yards and two touchdowns for Wisconsin, which has won 32 straight regular-season non-conference games, including all 24 under head coach Bret Bielema.
Montee Ball carried the ball 15 times for 88 yards and two scores. James White rushed for 95 yards and a touchdown on nine carries.
"We just try to go out there and execute our offense and, whoever touches the ball, they're going to try to make a big play," White said. "If it's over 600 yards, then that's what happens with our offense."
Dante Warren connected on 8-of-15 passes for 41 yards and two interceptions for the Coyotes (2-2), who had a two-game winning streak snapped.
"It is what it is. We took a beatdown by a superior squad, and we could kind of see it coming on film," South Dakota head coach Ed Meierkort said. "I was hoping it didn't explode the way it did, but I thought our guys competed pretty well."
The Badgers' second possession of the game resulted in a touchdown. Toon's 18-yard catch highlighted an eight-play, 60-yard drive that Ball capped with a five-yard rushing TD.
Warren was intercepted by Shelton Johnson on the ensuing South Dakota possession. Jared Abbrederis and Toon had big catches during a 10-play, 73- yard march, which Kyle French capped with a 25-yard field goal for a 10-0 lead.
Another Warren interception led to French missing a 50-yarder early in the second quarter. The Coyotes tried to gain some momentum, marching the ball down to the Wisconsin seven-yard line. South Dakota had to settle for a Kevin Robb 24-yard field goal.
White quickly responded with a 49-yard touchdown run to make it a 17-3 game.
After the Coyotes went three-and-out, Toon caught a 59-yard TD pass to give the Badgers a 24-3 margin with three minutes left until half.
Toon added a two-yard touchdown catch with 12 seconds left to make it 31-3.
Jared Abbrederis and Ball added touchdowns in the third quarter to give the Badgers a 45-3 lead.
Freshman running back Melvin Gordon scampered into the end zone from four yards out early in the fourth to make it 52-3.
South Dakota's first touchdown of the game came with under seven minutes to play, when Josh Vander Maten connected with Michael Neilson on a four-yard score.
Jeffrey Lewis' 41-yard TD run with just over two minutes remaining accounted for the final margin.
Wisconsin leads the all-time series by a 2-0 margin...The Badgers have now outscored their four foes by a combined count of 194-34...Wisconsin has won 12 straight home games...The Badgers open Big Ten play next weekend against Nebraska...Wisconsin is now 40-1 under Bielema when scoring at least 30 points in a game and 21-0 when scoring at least 40 points.