Ospreys wing Eli Walker will make his Wales debut in their Millennium Stadium clash against South Africa.
The 21-year-old fills the vacancy created by Alex Cuthbert, who is nursing an ankle injury, while centre Scott Williams partners his Scarlets colleague Jonathan Davies in midfield.
There is also a return for fly-half Rhys Priestland after he missed last season's entire title-winning RBS 6 Nations campaign due to an Achilles tendon injury.
Meanwhile, Cardiff Blues lock Bradley Davies has won coach Warren Gatland's vote to form the second-row pairing with Alun-Wyn Jones in a team captained by flanker Sam Warburton.
Flanker Dan Lydiate makes his first Wales appearance since the summer of 2012 following a serious ankle injury, with prop Gethin Jenkins winning his 99th cap.
On the bench, Gatland has found places for Perpignan back James Hook and Scarlets back-three player Liam Williams, who had been tipped by many to pip Walker and start instead of Cuthbert.
Walker, regarded as one of the deadliest finishers in the RaboDirect PRO12 competition, suffered a back injury last season that dashed any hope of him featuring in the Six Nations or Wales' subsequent two-Test summer tour of Japan.
"Eli has impressed for his region and while with us, and it's a great opportunity for him to make his mark in a very experienced side," Gatland said.
"We always say we like to test ourselves against the best, and Saturday is going to be just that with a huge game against South Africa first up."
Gatland noted that the Springboks were arriving in the UK off the back of an impressive Rugby Championship campaign, and said his side was knew that they would have to start well on Saturday.
"We go into the series as Six Nations champions, but we are looking forward to testing ourselves against the southern hemisphere sides and showing what we are can do, he said.
"Since we have been together, competition in the squad has been good, and it is great to have both Rhys and Dan back available for us."
After tackling South Africa, Wales also meet Argentina, Tonga and Australia this month.
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