Ospreys wing Eli Walker will make his Wales debut in Saturday's Millennium Stadium clash against South Africa.
The 21-year-old beat off competition from Liam Williams to take the place of Alex Cuthbert, who is ruled out with an ankle injury.
And with Jamie Roberts also absent, centre Scott Williams partners his Scarlets team-mate Jonathan Davies in midfield.
Rhys Priestland returns at fly-half after missing last season's entire Six Nations campaign with an Achilles injury.
And Cardiff Blues lock Bradley Davies will partner Alun-Wyn Jones in the second row, with Luke Charteris having to settle for a place on the bench.
British & Irish Lions flanker Dan Lydiate will make his first appearance for Wales since the summer of 2012, having missed nearly a year's international rugby because of injury.
Mike Phillips starts at scrum-half despite not currently having a club after he was sacked by Bayonne last week.
Walker - who would almost certainly have played in the 2013 Six Nations but for injury - is one of the deadliest finishers in the RaboDirect PRO12.
Coach Warren Gatland said: "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.
"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.
"The Springboks arrive in the UK off the back of their impressive Rugby Championship campaign, and we know that we need 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.
"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.
Wales: 15-L Halfpenny, 14-G North, 13-J Davies, 12-S Williams, 11-E Walker, 10-R Priestland, 9-M Phillips; 1-G Jenkins, 2-R Hibbard, 3-A Jones, 4-B Davies, 5-A W Jones, 6-D Lydiate, 7-S Warburton, 8-T Faletau.
Replacements: 16-K Owens, 17-P James, 18-S Andrews, 19-L Charteris, 20-J Tipuric, 21-L Williams, 22-J Hook, 23-L Williams