Agassi, 35, won the 60th title of his career by beating Gilles Muller of Luxembourg 6-4 7-5 in the final of the Los Angeles Open on Sunday.
"At this point in my career, I have to be extremely selective about the amount of matches that I play in preparation of the U.S. Open," Agassi said in a letter to the director of the Legg Mason tournament.
"I am sorry that I will not be there this year, but hope to return in 2006."
Agassi has played in Washington for the last 15 years and is a five-time champion. He was seeded number two this year behind Andy Roddick.
The two-week U.S. Open begins on August 29.