Top seed and defending champion will open campaign in his 12th US Open appearance against Jerzy Janowicz (Poland).
The 2016 US Open draw will be led by reigning champion Novak, followed by Olympic gold medalist Murray, Wawrinka and Nadal.
Novak has withdrawn from the Western & Southern Open due to recurring injury. His next event will be the US Open.
Nole suffered a tough 6-7 (4), 6-7 (2) defeat to Juan Martin del Potro at the Rio Olympics on Sunday evening.
The Serbian duo won their opening round match 6-2, 6-2 against Croatian combination of Marin Cilic and Marin Draganja.
Novak is a top seed and will open his campaign in singles competition against world no.145, Juan Martin del Potro (ARG).
Nole won his fourth Rogers Cup championship and 66th career trophy with a 6-3, 7-5 victory over no.3 seed Kei Nishikori in Toronto final.
Novak beat no.10 seed Gael Monfils 6-3, 6-2 on Saturday in the semi-finals and improved to a 50-4 match record on the season.
Novak’s bid for a fourth title at the Rogers Cup continued with a 7-6, 6-4 victory over no.5 seed Tomas Berdych on Friday.
Three-time former champion beat world no.129 Radek Stepanek 6-2, 6-4 to advance into the last eight in Toronto.