In the hours following the Spartans' September 18, 2010 victory over Notre Dame, Dantonio suffered a heart attack for which he was hospitalized, and received a coronary stent.

While he recovered, offensive coordinator Don Treadwell stepped in as acting head coach, leading the Spartans against Northern Colorado and Wisconsin.

The Spartans finished the regular season with eleven wins (tied the most to date in school history), one loss, and secured their first share of the Big Ten Championship in twenty years.

Le'Veon Bell became the first freshman running back at Michigan State to rush for more than 100 yards in his opening game.

The 2010 rendition of the Battle for the Megaphone Trophy proved to be one of the most memorable in the series, as Michigan State beat Notre Dame 34–31 in overtime.

[5] The Fighting Irish were the first to score, with quarterback Dayne Crist completing a seven-yard touchdown pass to Michael Floyd in the first quarter.

After multiple drives ending in turnovers for both teams, the Spartans got on the board with 2:22 left in the first half via a six-yard touchdown pass from Kirk Cousins to Keshawn Martin.

Instead, kick holder and punter Aaron Bates stood up to pass, and threw downfield to a wide open Charlie Gantt for the game-winning touchdown.

[7] With Coach Dantonio out for a second week following his heart attack, Michigan State hosted eventual co-champs Wisconsin at Spartan Stadium in the conference opener.

A clock-draining 15-play TD drive late in the 4th quarter put MSU up by 10 and set the tone for the rest of the Big Ten season.

MSU built on their lead in the third quarter with 2 touchdowns: first a 41-yard catch by Mark Dell, and then an 8-yard rush by Larry Caper.

With a ten-point deficit early in the fourth quarter, the Spartans were situated with a 4th and 6 at the Northwestern 30 yd line, but out of field goal range because of a heavy wind.

After punter Aaron Bates received the snap, he faked the punt and threw a 15 yd pass to Bennie Fowler for a first down.

During the post game interview, Coach Dantonio was asked about the play, when he replied "That's called Mousetrap, and we let 'em take the cheese."

The Wildcats went four and out on their next possession, but had another chance to tie the game after Edwin Baker ran for a 25 yd touchdown with a minute left to make it 35–27.