Millman plays in his first fourth round match at a major here after an impressive run so far in New York which includes four-set wins over the talented Fabio Fognini and Mikhail Kukushkin.
The Australian is known as an excellent mover and he is likely to be on the defensive for the majority of this match but he may need to adopt a more attacking approach if he is to trouble the five-time champion.
He will take confidence from his only previous meeting with Federer, where he competed well and took the first set before eventually losing 4-6, 6-4, 6-2 (Brisbane - 2015).
The third round meeting with Nick Kyrgios had all the makings of a potentially tricky contest but Federer produced his best display of the tournament so far in destroying the unpredictable Australian in straight sets, delighting the crowd with some moments of magic along the way.
Kyrgios' compatriot now stands in the 37-year-old's way and this will be an altogether different challenge; Millman does not possess the talent and shotmaking of Kyrgios but his best attributes are in his competitiveness and resilience.
Fans are already looking ahead to a potential quarter-final meeting with Novak Djokovic but Federer will not allow that to enter into his thinking and he will be aiming for another efficient straight-sets victory.
Millman has rightfully earned his place in the fourth round after some hard-fought victories over tough opponents but hard work alone will not be enough against an opponent such as Federer, who delivered a masterclass in shotmaking against Millman's fellow countryman Nick Kyrgios on Saturday.
Millman at least has the experience of having previously taken a set of Federer in the past, but doing so in a Grand Slam under the lights of Arthur Ashe is a different proposition. This is likely to be one step too far for the Australian with a straight-sets win for Federer in the offing.
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