Etzebeth partners Flip van der Merwe at lock for the South Africans, their battle with Alun Wyn Jones and Bradley Davies promising to be a hugely physical encounter.
It means there is no place in the Springbok squad for Toulon's Bakkies Botha.
"Line-outs are always very, very important," said Meyer, after announcing his side to face Wales.
"If you don't win your line-outs, particularly in these conditions, you won't get go forward ball.
"It will be a great challenge but our line-out has been working really well this year and hopefully we can take it to the next level."
On the omission of Botha, who boasts 76 international caps and a mountain of experience, Meyer added: "Bakkies hasn't been with us for a while, he only arrived late last night.
"The line-outs nowadays mean you can't just slot a guy straight in and I've got a lot of confidence in the youngsters. It would be unfair to throw Bakkies straight in and the other three have done well.
"I truly believe as far as locks go, Eben (Etzebeth) is one of the best in the world. We have a nice blend in terms of the team. There's a lot of experience at the top and underneath each experienced guy there's a youngster so I think we're doing the right thing for the long term."
Meyer saw his side compete well in the Rugby Championship, going down to the All Blacks in a thrilling encounter in Johannesburg. His frustration at being second best was clear to see at today's team announcement, the Springboks coach now looking forward to a clash with Wales.
"Last year our defence was awesome but we respect Wales and know this is not the Rugby Championship," he said.
"It's going to be an arm wrestle, if the conditions are great we want to score tries but your set piece has to be 100 per cent and we know Wales have a good scrum, a good line-out and have very big backs. It will be a difficult game.
"The thing about the Wales team is they have been together for quite some time. I mean this with respect - they have a simple game plan but they execute it brilliantly. There are not a lot of weaknesses there. They've got a great back three, a good defence and great ball retention. They will be difficult to play against. It will be a tough, tough Test match but we're looking forward to the challenge."
In the backs, Meyer has recalled experienced Japan-based duo Jacque Fourie and JP Pietersen at centre and wing respectively with Pat Lambie at full back.
"Pat's been playing good rugby. Without giving too much away, he's very safe under the high ball and offers something different in attack," said Meyer.
"He's happy to play there and I think that's the best choice for these conditions.
On the selection of the uncapped Malberhe, he added: "Frans is a specialist tight-head, he's proven himself in Super Rugby and is a quality player.
"I've known him since he was a school boy and I think he'll have a great game.
"We want to go out and win, that's the main objective."
Tickets to see Wales in action at the Millennium Stadium in the 2013 Dove Men Series - against South Africa, Argentina, Tonga and Australia - on consecutive weekends from 9th November are available online at www.wru.co.uk/tickets - prices from £25, £10 concession.
Wales Dove Men Series 2013 fixtures:
Wales v South Africa - Saturday, 9 November, Kick-Off 5.30pm - £70 / £60 / £40 / £25
Wales v Argentina - Saturday, 16 November, Kick-Off 2.30pm - £40 / £30 / £10 concession (U16) /£70 Family ticket 2 adults + 2 concession
Wales v Tonga - Friday, 22 November, Kick-Off 7.30pm - £25 / £10 concession/ £60 Family ticket 2 adult + 2 concession/ Minis/Juniors/Schools offer, with every 8 concessions purchased 2 adult tickets free
Wales v Australia - Saturday, 30 November, Kick-Off 5.00pm - £70 / £60 / £40 / £25