In addition to the new caps in the starting team, there are a further five possible new caps named amongst the replacements.
The pack has an experienced foundation through the leadership of captain Best and he will be accompanied in the front row by Tom Court at loosehead, starting his first game for Ireland, and Tony Buckley who starts at tighthead.
Bob Casey will end a nine-year break between his last cap, which was also against Canada in 2000, when he lines out at Thunderbird Stadium in the second row with Mick O'Driscoll.
There are two Test debutants is the back row where Connacht captain John Muldoon and Munster openside Niall Ronan join battle-hardened number 8 Denis Leamy.
The back-line contains four new caps, the first being out-half Ian Keatley who will partner Ireland's most-capped scrum half Peter Stringer.
Outside Keatley, Ian Whitten and Darren Cave will form an all-Ulster centre combination.
Munster will be supplying the wingers for the game with Barry Murphy lining out on the right wing and debutant Ian Dowling named on the left with Gavin Duffy completing the back-three.
IRELAND Squad (v Canada, Saturday May 23, Thunderbird Stadium, Vancouver, kick-off 2pm local time/10pm Irish time (live RTE Two):
15. Gavin Duffy (Galwegians/Connacht)
14. Barry Murphy (UL Bohemians/Munster)
13. Darren Cave (Belfast Harlequins/Ulster)*
12. Ian Whitten (Ballymena/Ulster)*
11. Ian Dowling (Shannon/Munster)*
10. Ian Keatley (Galwegians/Connacht)*
9. Peter Stringer (Shannon/Munster)
1. Tom Court (Malone/Ulster)
16. Sean Cronin (Buccaneers/Connacht)*
17. Mike Ross (Harlequins)*
18. Ryan Caldwell (Dungannon/Ulster)*
19. Donnacha Ryan (Shannon/Munster)
20. Eoin Reddan (London Wasps)
21. Niall O'Connor (Belfast Harlequins/Ulster)*
22. Denis Hurley (Cork Constitution/Munster)*
* Denotes uncapped player