"Now we have possibly the changing of the guard. You have those top two who are now losing ground to the likes of (Novak) Djokovic and Murray and (Juan Martin) del Potro," Agassi told reporters in Hong Kong by phone from Las Vegas.
Nadal has struggled with injuries since his stunning exit in the fourth round of the French Open. Federer won the French and Wimbledon, breaking Pete Sampras' record of 14 Grand Slams, but was beaten in the U.S. Open final by 21-year-old Argentine del Potro. It was the first Grand Slam won by a player other than Federer or Nadal since Djokovic won the 2008 Australian Open.
Agassi, who preceded Federer in winning all four grand slam tournaments over his career, believes the Swiss "still has the chance to do some more special things," but the 28-year-old's chances are diminishing with age.
Agassi, who was promoting his upcoming exhibition match against Sampras in the Chinese gambling enclave Macau on Oct. 25, worried that Nadal's injuries may be chronic.
"If you're struggling with your knee, it tends to be recurring and not to be easy to do, so I got to believe he'll struggle with it probably for his career," Agassi said.
Agassi said the 22-year-old Murray is the man most likely to be the dominant figure over the next few years. The world No. 3 is still seeking his first Grand Slam title.
"From a talent standpoint, Murray is a person who should win multiple Slams," Agassi said.
"When I look at his game compared to the other players, he has what it takes to win and to win against anybody on any surface."