Three other players - Ian Madigan, David Kilcoyne and Iain Henderson - will start for Ireland for the first time having previously been capped off the bench.
There are a further three uncapped players among the replacements with forwards Mike Sherry, Jamie Hagan and Tommy O'Donnell all included.
Mike Ross is the most capped player in the selected team and he packs down in the front row with Richardt Strauss and Kilcoyne.
Mike McCarthy and Devin Toner form the second row pairing with Henderson and Chris Henry on either side of Ireland's summer tour captain Peter O'Mahony in the back row.
Speaking ahead of the game, interim head coach Les Kiss said: "We've had a good week of preparation and the players have settled well in Houston.
"This is a young team with five players starting for the first time and we are under no illusions as to the challenge posed by an experienced and improving USA Eagles team."
The Test match will be broadcast live on TG4 with the 'Rugbaí Beo' coverage getting underway at 1.20am (Sunday morning). The channel are also providing a live worldwide stream on www.tg4.tv.
There will be a full replay of the game on TG4 later that day at 12.05pm. In America, the Universal Sports Network will be showing the Houston encounter live.
Highlights and behind the scenes footage from the Irish summer tour so far can be seen on www.youtube.com/O2Rugby.
IRELAND Team & Replacements (v USA, BBVA Compass Stadium, Houston, Summer Tour Test, Saturday, June 8, kick-off 7.45pm local time/1.45am Irish time):
15. Robbie Henshaw (Buccaneers/Connacht) *
14. Fergus McFadden (Old Belvedere/Leinster) 17
13. Darren Cave (Belfast Harlequins/Ulster) 3
12. Stuart Olding (Belfast Harlequins/Ulster) *
11. Simon Zebo (Cork Constitution/Munster) 5
10. Ian Madigan (Blackrock College/Leinster) 2
9. Isaac Boss (Terenure College/Leinster) 15
1. David Kilcoyne (UL Bohemians/Munster) 6
2. Richardt Strauss (Old Wesley/Leinster) 2
3. Mike Ross (Clontarf/Leinster) 29
4. Mike McCarthy (Buccaneers/Connacht) 10
5. Devin Toner (Lansdowne/Leinster) 5
6. Iain Henderson (Ballynahinch/Ulster) 5
7. Chris Henry (Malone/Ulster) 6
8. Peter O'Mahony (Cork Constitution/Munster) (capt) 14
16. Mike Sherry (Garryowen/Munster) *
17. Tom Court (Malone/Ulster) 30
18. Jamie Hagan (Old Belvedere/Leinster) *
19. Dan Tuohy (Ballymena/Ulster) 5
20. Tommy O'Donnell (UL Bohemians/Munster) *
21. Paul Marshall (Belfast Harlequins/Ulster) 1
22. Paddy Jackson (Dungannon/Ulster) 3
23. Felix Jones (Shannon/Munster) 3
* Denotes uncapped player