On September 19, 2010, just hours after a stunning fake field goal touchdown pass gave MSU a 34–31 overtime victory over Notre Dame, Dantonio checked himself into a hospital after noticing chest pains. He later suffered a heart attack. He had a stent implanted in a blocked artery near his heart. His doctor stated that the damage was minimal and that Dantonio was expected to make a full recovery. Offensive coordinator Don Treadwell became acting head coach while Dantonio recovered.
On September 30, after Dantonio had stated that he would be coaching the next game from the press box and just two days before Michigan State played Wisconsin, Dantonio was admitted back into the hospital as a blood clot was found in his leg. Dantonio had to watch the game from his hospital room. He was reportedly released from Sparrow Hospital around noon on October 4, 2010. On October 9, Dantonio coached his first game since his heart attack against rival Michigan. Michigan State won the game, 34–17, in Ann Arbor.
The Spartans under Dantonio continued to win and on November 20 reached 10–1 on the season, winning all home games for the first time during his tenure. It was just the third time in school history that Michigan State had won 10 or more games in a season, the other two seasons being those of 1965 and 1999. On November 27, 2010, Dantonio's Spartans defeated Penn State 28–22 in Happy Valley to finish the season 11–1 and clinch a share of the Big Ten Championship for the first time since 1990. On December 5, 2010, MSU announced that the Spartans were selected to play in the Capital One Bowl on January 1, 2011, against Alabama (ranked 15th in the BCS standings). The Spartans lost to the Crimson Tide 49–7 and finished 11–2.