The game also marks the final match for Joe Schmidt on Irish soil.
Best, who will retire after the Rugby World Cup, leads a much-changed Ireland team against Wales in the final Guinness Series Test of the summer.
Leinster’s Cian Healy and Tadhg Furlong join the Ireland captain in the front row with James Ryan and Jean Kleyn packing down in the second row.
Jack Conan starts at No.8 with CJ Stander coming into the back row at blindside flanker and Josh van der Flier on the openside.
Johnny Sexton makes his seasonal debut and is joined in the half-backs by Conor Murray. Bundee Aki starts at No.12 with Robbie Henshaw coming in at No.13.
— Irish Rugby (@IrishRugby) September 5, 2019
Keith Earls is also back on the left wing, with Jordan Larmour on the right and Rob Kearney at full-back.
Sean Cronin is in line to win his 70th cap from the bench – he’s joined by Dave Kilcoyne, Andrew Porter, Iain Henderson and Rhys Ruddock as the forward cover. Luke McGrath, Jack Carty and Garry Ringrose are the replacement backs.
Ireland Team vs Wales, Guinness Series 2019, Aviva Stadium, Saturday, September 7, 2pm
15. Rob Kearney (Leinster) 91 caps
14. Jordan Larmour (Leinster) 15 caps
13. Robbie Henshaw (Leinster) 37 caps
12. Bundee Aki (Connacht) 19 caps
11. Keith Earls (Munster) 77 caps
10. Jonathan Sexton (Leinster) 83 caps
9. Conor Murray (Munster) 73 caps
1. Cian Healy (Leinster) 90 caps
2. Rory Best (Ulster) 119 caps CAPTAIN
3. Tadhg Furlong (Leinster) 35 caps
4. James Ryan (Leinster) 18 caps
5. Jean Kleyn (Munster) 2 caps
6. CJ Stander (Munster) 32 caps
7. Josh van der Flier (Leinster) 18 caps
8. Jack Conan (Leinster) 15 caps
16. Sean Cronin (Leinster) 69 caps
17. Dave Kilcoyne (Munster) 30 caps
18. Andrew Porter (Leinster) 17 caps
19. Iain Henderson (Ulster) 47 caps
20. Rhys Ruddock (Leinster) 22
21. Luke McGrath (Leinster) 13 caps
22. Jack Carty (Connacht) 6 caps
23. Garry Ringrose (Leinster) 23 caps