Before the 2010 season, Ponder was named to the Maxwell Award watch list. Florida State launched a campaign promoting Ponder as a Heisman Trophy candidate in July 2010. During the 2010 season, Ponder battled numerous setbacks to his health, including a swollen bursa sac in his throwing elbow. He re-injured the elbow numerous times during the season, and had to have it drained three times.
Ponder's 2010 season, his senior year and only year under coach Jimbo Fisher, was his most successful. Ponder was the first Seminole quarterback since Chris Weinke in 1999 to lead his team to victories over both its in-state rivals, Miami and Florida. He also won the 2010 James Tatum award, given to the nation's top student-athlete, and a National Football Foundation Scholar-Athlete Award. He also won the Bobby Bowden Award presented to the top student athlete among FBS schools. Ponder graduated from Florida State in two and a half years with a degree in finance and a 3.73 GPA, then an MBA, and is studying for his second graduate degree, in sports management. At the 2011 Under Armour Senior Bowl, Ponder won MVP honors after throwing for 2 touchdowns and leading the South to a win over the heavily favored North.