The Northern Irish pair will play Jim Furyk, winner of all his five games at the Presidents Cup last year, and Brandt Snedeker, who last Sunday pulled off a £7million double of FedEx Cup and Tour Championship victories.
In the second game Luke Donald and Sergio Garcia, both unbeaten in foursomes in the match, take on Phil Mickelson and Keegan Bradley, like Snedeker a cup rookie.
Lee Westwood has been given Italian Francesco Molinari as his partner - they face Zach Johnson and another debutant in Jason Dufner - while Tiger Woods is kept until last by home captain Davis Love.
Woods and Steve Stricker will take on Justin Rose and Ian Poulter, who yesterday spoke of wanting to "kill" his opponents in the biennial competition.
Poulter has faced Woods twice before and lost both times, but has won eight of his other nine games.
The action starts at 7.20am local time and the foursomes will be followed by afternoon fourballs.
Woods said: "Strick and I are very comfortable together. We've had some pretty good success over the years and we both have been playing well.
"Our captain said that would be a good fit and he wanted us out there to anchor.
"We know each other's game and we practise a lot together at tournaments. We know what to expect from each other."
Mickelson said: "I'm really excited to play with Keegan - we have been wanting it for a while.
"We have a very difficult match. Luke I don't think has ever lost in foursomes and we are hopefully going to change that."
Snedeker stated: "[I'm] really excited. Jim is playing great and a great guy to lean on. He's got so much experience."
McIlroy said: "I can't wait. Leading the side off we are going to go out there and get the blue on the board early.
"It is a great honour to lead Europe out and to be honest they are not the opponents we were expecting.
"We know that their team is so strong all the way through, but it was a little surprise to see a rookie in their first group."
McDowell added: "We are going to use the world number one's power and precision and I will just knock a few tap-ins in.
"I am very proud to be playing alongside my great friend and the greatest player on the planet.
"I was expecting Phil and Keegan to go first, but obviously Davis has his strategies.
"Tomorrow morning's session is hugely important and Jose Maria has stressed that. We really feel that it is very important to make a fast start.
"We are pretty pumped for this whole thing."
Donald said: "We've obviously both got unbeaten records in foursomes and we have played well together in the past.
"It should be a great match against two very good players. They obviously know each other well, but Sergio and I do and we have had some great success together.
"Obviously Phil has a lot of experience and Keegan is a rookie, but it's not a pairing that surprises you because they play a lot of golf together.
"But we've had some success against Phil before and hopefully we can again tomorrow.
"It should be a great atmosphere with Phil playing and hopefully I will get some support as I live in Chicago and Sergio obviously has some special memories from here." He was runner-up to Woods in the 1999 USPGA.
Garcia added: "He's my best friend on tour and we get on great in foursomes together.
"We are going to try as hard as we can to bring back a point for the European team."