Mitchell Marsh, who presented a case of being almost undroppable after scoring a century during Australia's loss in the third Test at Headingley, has been picked alongside the returning Cameron Green.
Marsh had replaced Green through injury at Headingley.
Zero Wicket analysis has recently revealed Manchester is a spinner's graveyard unless your name is English spinner Moeen Ali, who suggested during the week Australia would be missing a trick to leave Murphy out.
Australia will benefit from the move in the batting stakes though, with Marsh, Green and wicket-keeper Alex Carey to bat at six, seven and eight, before Pat Cummins and Mitchell Starc bat at nine and ten.
"Nathan Lyon is the greatest offspinner we've ever had so it's not quite apples for apples," Cummins said in explaining the call to leave Murphy out.
"We are really excited by Todd, we think he's fantastic. I would have loved to use him a bit more last week, (but) conditions just favoured pace bowling.
"We played a Test in Hobart last year in the Ashes where Nath didn't bowl an over. It's all conditions based.
"We are really excited by Todd, we think he's a gun, we love having him around, he's got a big future. It was more conditions the way I used him, as opposed to how he bowled."