The 53-year-old believes that the Melbourne heat - due to peak at 97 degrees Fahrenheit on Thursday - will take its toll on the Swiss, who has won the tournament four times during his illustrious career.
Federer opens his campaign against Benoit Paire later in the day session of the second day.
"Djokovic and Murray to me are the two biggest favourites and Roger is going to have a tougher time winning majors, particularly if the heat becomes a factor," said McEnroe.
"At his age it's not easy to bounce back as quickly and play best-of-five sets, but it's also very difficult for anyone besides those guys to be able to beat at least two if not three of them, so that would be very unlikely."
McEnroe reached the semi-final of the Australian Open in 1983.