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 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.
"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."