The Nationals open their season at 1:05 p.m. EDT April 5 against the visiting Philadelphia Phillies.
Obama's appearance is a continuation of a presidential traditional begun 100 years ago when William Howard Taft tossed the first pitch on April 14, 1910, to open the Washington Senators' game with the Philadelphia Athletics.
"Opening day of the baseball season is a special event for our country and its importance has been reinforced by the 100-year history of presidential participation," baseball Commissioner Bud Selig said in a statement.
"I am proud that President Obama will continue the long presidential tradition of throwing out the first pitch of opening day in Washington, D.C."
The Nationals plan to start left-handed John Lannan, 9-13 last season, and the Phillies are going with right-hander Roy Halladay, 17-1-0 for Toronto last year.