Kaepernick played college football for the University of Nevada (Reno) Wolf Pack. At Nevada, Kaepernick twice was named the Western Athletic Conference Offensive Player of the Year, and he was the Most Valuable Player of the 2008 Humanitarian Bowl. In the 2011 NFL Draft, the San Francisco 49ers selected Kaepernick in the second round with the 36th overall pick.

In the middle of the 2012 season, Kaepernick became the full-time starter as the 49ers advanced to the NFL playoffs for the second straight season. After beating the Atlanta Falcons in the NFC Championship 28-24, he led the 49ers to their first Super Bowl since 1994.