The 22-year-old has won both his caps off the bench in the warm-up defeats to France and England.
However Murray, who has yet to play in the Heineken Cup, has got the nod ahead of Isaac Boss and Eoin Reddan to start.
"Conor's been going well in training and we said we'd judge it off that. If we're to know more about him, now's the time to know," said Ireland coach Declan Kidney.
"He deserves a go and we think he's good enough to start. It's a big call given it's our first game in the World Cup, but what he's been doing merits his inclusion."
Murray will team up with Jonathan Sexton at half-back, with Reddan and Ronan O'Gara on the bench.
Geordan Murphy and Shane Jennings also start against the Eagles, with Sean O'Brien and Rob Kearney omitted from the 22 as a precaution.
The Leinster duo have been passed fit from their respective knee and groin injuries but Kidney, mindful of the clash with Australia next Saturday, has given them another week to recuperate.
"Sean is fit to play, medically he has been given the okay," said Kidney.
"But I've seen injuries like that before and he'll benefit from getting absolute fitness back.
"I believe in the squad too. Shane Jennings has been going well in training and has a bit of match time under his belt last month.
"Rob is up and training but I want him to get up to full speed a bit more often.
"Once he does that he'll be fine. He showed against Scotland last month that he is able to come straight back in after a number of months out.
"The fact he's not playing on Sunday doesn't rule him out against Australia by any means."
While O'Brien and Kearney are rested, Gordon D'Arcy has been restored at inside centre having recovered from the calf injury which delayed his arrival in New Zealand.
The most unfortunate member of the squad is Andrew Trimble, who is demoted to the bench despite being Ireland's most dangerous player during the warm-up internationals.
Tommy Bowe and Keith Earls have been named on the wings and Trimble will feel a sense of injustice at his exclusion.
"We have three wingers who have been going well. Keith has had three games but two of those have been in the centre," he said.
"He's only had one run on the wing and he's done well in that position in the past.
"Tommy comes back from injury and has played only one game.
"Andrew's losing out and he's unlucky. He's had four games and has done very well. It's a good position for us to be in."
Ireland team v USA: 15 G Murphy, 14 T Bowe, 13 B O'Driscoll (capt), 12 G D'Arcy, 11 K Earls, 10 J Sexton, 9 C Murray, 1 T Court, 2 R Best, 3 M Ross, 4 D O'Callaghan, 5 P O'Connell, 6 S Ferris, 7 S Jennings, 8 J Heaslip.Replacements: 16 J Flannery, 17 T Buckley, 18 D Ryan, 19 D Leamy, 20 E Reddan, 21 R O'Gara, 22 A Trimble.
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