The Serbian ace is in the final eight at a Grand Slam for the 28th consecutive time, surpassing Jimmy Connors for second best streak ever.
Novak defeated no.14 seed Dominic Thiem to reach the Miami Open presented by Itaú last eight. He next faces Tomas Berdych (CZE, 7).
The top seed beat Gilles Simon 6-3, 6-7 (1), 6-4, 4-6, 6-3 on Rod Laver Arena in a hard-fought four hours, 32-minute fourth round clash on Sunday.
Top seed lost first two sets but fought back to beat Kevin Anderson 6-7 (8), 6-7 (8), 6-1, 6-4, 7-5 and reach the last 8.
The top seed advanced into the Roland Garros last eight with a 6-1, 6-2, 6-3 triumph over Richard Gasquet (FRA, 20) in two hours.