Jonathan and James Davies will become the first set of brothers since 2006 to start for Wales when they feature against England on Saturday.
Wales head coach Warren Gatland has named Scarlets openside flanker James alongside back-row colleagues Aaron Wainwright and Ross Moriarty for the World Cup warm-up clash in Cardiff.
Jonathan, meanwhile, partners Hadleigh Parkes in midfield as Wales look to bounce back from a 33-19 loss to England at Twickenham last weekend.
They are the first set of brothers to play alongside each other for Wales since Jamie and Nicky Robinson 13 years ago.
James Davies replaces Justin Tipuric, while two other changes from the England defeat see fly-half Dan Biggar come in for an injured Gareth Anscombe and lock Jake Ball replacing Adam Beard.
Biggar starts with Anscombe having suffered a World Cup-ending knee ligament injury at Twickenham.
And Cardiff Blues forward Josh Navidi is among the replacements, along with his Blues colleague and fly-half Jarrod Evans.
Gatland said: “This weekend is another opportunity for us to take the field, test ourselves and continue our preparation for Japan.
“It is a little over five weeks until we kick off our campaign in Toyota against Georgia, and it is important we are fully prepared and rugby-ready by then.
“We were disappointed to get the loss last weekend, so it is important we step it up on Saturday and put in a big display in front a of a packed Principality Stadium.
“The squad are looking forward to getting back out there, taking another step towards the World Cup and putting in a big performance.”
Wales are unbeaten at the Principality Stadium since world champions New Zealand toppled them in November 2017, since when they have reeled off 10 successive victories.
Anscombe looks unlikely to play next season, with Gatland confirming that he will require surgery.
BRODYR 🦊 James and Jonathan Davies will be the first pair of brothers to play alongside each other for Wales since Jamie and Nicky Robinson in 2006. pic.twitter.com/S0dDdU9LRf— Welsh Rugby Union 🏉 (@WelshRugbyUnion) August 15, 2019
“He has done the ACL (anterior cruciate ligament) and the meniscus as well,” Gatland said.
“Unfortunately, he is going to require surgery and it’s probably going to keep him out for most of the season.”
Tipuric and Beard, meanwhile, have been left out as precautions this weekend.
“Justin Tipuric has got a little bit of a knock on his ankle last weekend,” Gatland added. “He’s fine, but we are just resting him as a precaution.
“Adam Beard has got a sore wrist. He is probably alright for Saturday, but we’ve made that change early on.”
Eddie Jones confirmed his 31-man squad for the forthcoming Rugby World Cup on Monday, and said he felt for the “disappointed players” who had missed out on selection.
The England head coach softened the blow by announcing that they “could get their opportunity later down the track” and should be ready to step in for any injured players.
Flanker Lewis Ludlam and uncapped wing Ruaridh McConnochie earned shock call-ups to Jones’s squad, while centre Ben Te’o was a surprise omission.
Eddie Jones explained Ben Te’o’s shock omission from England’s World Cup squad by declaring he was simply not good enough to be selected.
Until he was involved in an altercation with team-mate Mike Brown during a social event at the squad’s warm-weather camp in Treviso a fortnight ago, Te’o was considered a certainty for Japan 2019.
The 32-year-old Test Lion was an ever-present under Jones, was picked to play for England even when having spent months out injured and toured Australia in 2016 before having turned out for his club Worcester.
But in a dramatic fall from grace, he has been overlooked for the 31-man squad that will depart for the tournament on September 8, losing out to the unheralded Piers Francis who has been limited to five caps.
Jones said: “I’m not going to go into reasons why Ben Te’o hasn’t been selected. We’ve had that conversation with Ben. He understands it.
“Whether he agrees with it is another matter. But we’ve had that discussion and he’s not in our top 31 players at the moment.”
Sevens specialist and 2016 Olympic silver-medallist Ruaridh McConnochie continues a remarkable year by being present as the only uncapped player on the strength of an impressive end to his debut season for Bath.
Flanker Lewis Ludlam has been plucked from obscurity at Northampton in another pick that would have been unthinkable as recently as May and he profits from Brad Shields’ foot injury.
Hooker Jack Singleton and scrum-half Willi Heinz made their debuts in Saturday’s rout of Wales and are also chosen.
“Firstly, I think it’s always nice to bring new blood in. It freshens everything up. When you have the enthusiasm that young players do, it adds to the squad,” Jones said.
“Ruaridh we’ve been watching quite closely through the club season. I was impressed by him.
“Once he came into camp, he cemented our impression of him. He’s a very good worker, a very good communicator.
“He’s a mature boy who has played a number of positions, so he was a pretty easy selection in the end.
“Lewis absolutely came from nowhere. We’ve been watching him in club rugby. He did particularly well and again we thought we’d roll the dice and bring him into camp to see what he could offer.
“Every week he got better and against Wales we saw a display that’s only just the start of his career.”
Jones has gambled by taking only two scrum-halves – with Heinz deputising for Ben Youngs, who is first choice in the position – while George Ford will offer emergency cover.
The decision to pick just five props means Harry Williams misses out, Kyle Sinckler and Dan Cole travelling as the two tightheads to complement looseheads Mako Vunipola, Joe Marler and Ellis Genge.
“We’d like to take three in every specialist position but that would leave us short in other positions, so we’ve decided to go with two at scrum-half and two at tighthead,” Jones said.
“There are risks involved in it, but there are risks involved in other positions as well.
“We’ve got contingency in George Ford who has played a little bit at half-back.
“He’s been doing some training there and he’ll continue to do that. If we need a third half-back then we feel he can fill the role for a period of time.”
Tom Curry (shoulder), Jack Nowell (ankle), Henry Slade (knee) and Sam Underhill (toe) are expected to recover from their injuries before England set off for the World Cup.