Full-back Rob Kearney and scrum-half Tomas O'Leary start following lengthy spells of rehabilitation, while hooker Jerry Flannery is named on the bench.
Kearney has not played since last year's autumn Test against New Zealand when he sustained a knee injury.
"Rob will be judged by a certain standard and there will be comments that he hasn't played for a while," said head coach Declan Kidney.
"All we ask is that he gives everything. He'll work through it and whether he has a storming game or a not so good one, it's just one game.
"When you're out injured for a long time, you just want to be able to get back on the pitch.
"If you can do that in a Test it's a bit daunting, but also an added bonus."
O'Leary made his last Ireland appearance against France in February before also being ruled out for the remainder of the season with an eye problem.
Flannery's long battle with a calf injury that forced him to miss the autumn and RBS 6 Nations looks over after the Munster hooker was named on the bench.
All three are first choice in their positions when fit but desperately need matches to sharpen up in time for the World Cup.
Leinster's Leo Cullen leads a largely second string line-up in the first outing of Ireland's four-Test summer series.
None of the pack are likely to start the World Cup opener against the USA on September 11, but Cullen, Denis Leamy and Tony Buckley supply experience.
Connacht blindside flanker Mike McCarthy is the only uncapped player in the starting XV with winger Felix Jones of Munster included among the replacements as the other debutant.
The bench contains vast experience with Flannery, Marcus Horan, John Hayes and Mick O'Driscoll all veterans.
With fitness doubts over Gordon D'Arcy and to a lesser extent Brian O'Driscoll, Leinster rookie Fergus McFadden is given the nod at outside centre.
While Kidney is juggling the need to test out combinations and give certain players crucial game time, he insists beating Scotland remains the priority.
"When you play a Test match there's no holding back. You either go for it or you don't," he said.
"If you operate at only 80 or 90% you actually increase your chances of picking up a knock.
"It's a Test match and that's the way we're approaching it - we want to go out there and get a win
"First and foremost every time you wear the green jersey you want to win the game.
"That's why we have a good, experienced team with just one new cap in it.
"We also want to try new combinations and from there get our base level right to see where we are come Saturday."
Gilbert has released a new line of rugby cleats. The Gilbert Virtuo 8S is part of the exciting new product. Check it out.
The entire All Blacks apparel line has been updated for 2013/14. Check out the New Zealand All Blacks polo.
The Nike Tiempo is a solid rugby cleat and one of few styles still made from full-grain natural leather.
The Gilbert Blitz 8S rugby cleat is a great cleat at a great price of $69.99. Get a new pair of cleats today.
A cool looking all black rugby cleat with the high performance adidas is known for. Get in the Gear!
Wear the crest of the British and Irish Lions on your t-shirt. A great look for the summer.
The All Blacks Performance t-shirt is black with hints of blue from the training jersey. Very Cool.
The New Zealand All Blacks training jersey for 2013/14. Get in the Gear!
The USA Rugby Pro Alternate rugby jersey is perfect for any fan of the Eagles. Get yours to wear during the summer Test matches.
The NEW All Blacks 2013/14 jersey has arrived at World Rugby Shop. Dare to wear the colors of the All Blacks.