Head coach Eddie Jones will hand Fiji-born No.8 Hughes his first start for England having lost Billy Vunipola to injury, the Saracens back-rower facing at least three months out with a knee injury suffered in last week's 27-14 win over Argentina.
The other alteration sees Yarde come in on the right wing in place of the suspended Elliot Daly with Jonny May switching flanks to make way for the Harlequins flyer.
Other than the two changes he was forced to make, Jones has stuck with the rest of the team that started against the Pumas last week, while the bench remains the same as winger Semesa Rokoduguni and lock Dave Attwood miss out on a place in the squad.
Victory over Australia will complete a remarkable year for Jones and the Red Rose after 12 straight victories, a run that includes a 3-0 series whitewash of the Wallabies Down Under.
Jones feels his home nation have improved since England faced them in the summer and has warned his players to be on their guard against an opponent seeking revenge.
"Australia have improved significantly since we last played them. The enduring feature of Australian rugby is their cleverness. They look like they are doing one thing and they do the other. They have got some quite clever two-phase variation plays and we are going to need to be on our guard," Jones said.
"We want to make the game into a physical contest but we also need to be flexible and adaptable like we were against Argentina and if we do that we'll put ourselves in a good position to win the game.
"We've played three Test matches on the trot which is important because it replicates a World Cup pool. You get through the pool you then need to win every game to win the World Cup.
We've won three from three so it's a great dress rehearsal for the World Cup. We need to win this game to progress to the next stage."