The 17-time Grand Slam champion was ranked No. 1 in the ATP rankings released Monday. Defending champ Novak Djokovic is seeded second and Olympic gold medallist Andy Murray third.
With Rafael Nadal out with knee problems, fellow Spaniard David Ferrer is the No. 4 seed.
Milos Raonic of Thornhill, Ont., is seeded No. 15.
Federer has won five titles at Flushing Meadows, tied for most in the Open era. He won Wimbledon this year and returned to the top of the rankings.
John Isner will be the highest-seeded American at No. 9. Andy Roddick is 20th, Mardy Fish is 23rd and Sam Querrey 27th among the 32 seeded players announced Tuesday by the U.S. Tennis Association.
The draw will be Thursday and the tournament begins Monday.