On August 4, 2011, Whitner signed with the San Francisco 49ers. After previously announcing on Twitter that he would be going to the Cincinnati Bengals, he changed his mind and signed with San Francisco. He agreed to a three-year, $11.75 million deal with $4 million guaranteed. After his performance in his first year as a 49er, he was named to the USA Today All Joe Team During the 2011 playoffs, Whitner became famous for making vicious hits like against New Orleans Saints running back Pierre Thomas as he was driving for a touchdown. The hit forced a fumble recovered by the 49ers and took Thomas out for the rest of the game.