Cardiff Blues stars Alex Cuthbert, Cory Allen, Matthew Rees and Josh Turnbull will all represent Wales in their opening game in South Africa against Eastern Province Kings in Port Elizabeth on Tuesday (kick-off 7pm local time).
Warren Gatland's starting XV includes four uncapped players, with Matthew Morgan lining up at full-back, Steven Shingler at inside centre and Jordan Williams on the wing.
They are joined in the backline by Cardiff Blues duo Alex Cuthbert and Cory Allen as well as James Hook and Rhodri Williams at half back.
In the pack Paul James is named alongside Scott Baldwin and Rhodri Jones in the front-row with Jake Ball and Ian Evans in the second-row.
Captain Dan Lydiate is joined by new Cardiff Blues back row Josh Turnbull at flanker with Dan Baker at No 8.
On the bench Cardiff Blues hooker Matthew Rees is named in a Wales squad for the first time since February 2013.
Uncapped Gareth Davies is named amongst the replacements along with George North and Liam Williams.
WALES TEAM TO PLAY EASTERN PROVINCE KINGS:
Matthew Morgan (Ospreys), Alex Cuthbert (Cardiff Blues), Cory Allen (Cardiff Blues), Steven Shingler (Scarlets), Jordan Williams (Scarlets), James Hook (Perpignan), Rhodri Williams (Scarlets), Paul James (Bath), Scott Baldwin (Ospreys), Rhodri Jones (Scarlets), Jake Ball (Scarlets), Ian Evans (Ospreys), Dan Lydiate (Capt) (Racing Metro), Josh Turnbull (Cardiff Blues), Dan Baker (Ospreys).
Replacements: Matthew Rees (Cardiff Blues), Aaron Jarvis (Ospreys), Samson Lee (Scarlets), Luke Charteris (Perpignan), Aaron Shingler (Scarlets), Gareth Davies (Scarlets), George North (Northampton Saints), Liam Williams (Scarlets).