The 21-year-old has been given his chance after injury ruled out wing Alex Cuthbert from the first of Wales’ four November internationals.
Meanwhile Rhys Priestland returns at flyhalf after missing all of Wales’s Six Nations title-winning campaign last season with an Achilles injury.
British and Irish Lions skipper Sam Warburton again captains the side from the back-row where Dan Lydiate, one of the stars of the combined side’s 2-1 series win in Australia this year, makes his first Wales appearance since 2012 following an ankle injury.
Walker has long been regarded as one of the best finishers in the Celtic League but a back injury ruled him out of both the Six Nations and Wales’s two-Test pre-season 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 after the team was announced on Tuesday.
As for the return of Priestland and Lydiate, Gatland added “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.”
Gatland has overseen three Six Nations titles, two Grand Slams and a World Cup semi-final appearance since taking charge of Wales in 2008.
But Wales’s record in that same period against the southern hemisphere giants of New Zealand, South Africa and Australia has been dire, with just one win – against Australia in 2008 – compared to 20 defeats.
However, their poor run against the Springboks – one win in 26 Tests stretching back 107 years – was established long before the New Zealander took charge of Wales.
South Africa have arrived in Europe on the back of finishing highly creditable second behind world champions New Zealand in the southern hemisphere Rugby Championship and are sure to provide tough opposition.
“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,” said Gatland.
“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,” he added.
As well as the Springboks, Wales’ November programme also features Cardiff internationals against Argentina, Tonga and Australia.
South Africa are due to name their side on Wednesday.
15 Leigh Halfpenny, 14 George North, 13 Jonathan Davies, 12 Scott Williams, 11 Eli Walker, 10 Rhys Priestland, 9 Mike Phillips, 8 Toby Faletau, 7 Sam Warburton (captain), 6 Dan Lydiate, 5 Alun Wyn Jones, 4 Bradley Davies, 3 Adam Jones, 2 Richard Hibbard, 1 Gethin Jenkins
Substitutes: 16 Ken Owens, 17 Paul James, 18 Scott Andrews, 19 Luke Charteris, 20 Justin Tipuric, 21 Lloyd Williams, 22 James Hook, 23 Liam Williams