Iain Henderson is also unable to make the trip to Cardiff, meaning Beirne plays for the first time in this campaign.
Beirne will be partnered in the second row by James Ryan, with Quin Roux on the bench as a replacement. They are right wing Keith Earls, scrum-half Conor Murray, flanker Peter O'Mahony and No.8 CJ Stander.
The front row remains unchanged with Cian Healy and Tadhg Furlong either side of captain Rory Best, who will make his final championship appearance.
Kearney had to pull out of their game against France at the last minute and was replaced by Jordan Larmour, who now drops to the bench.
Schmidt admitted he would have preferred not to have to throw Beirne in straight away.
"That's been a really positive challenge for us throughout the Six Nations, to still try to get some cohesion. If it was me I'd be concentrating on playing Scotland", joked Gatland. "He knows his Scarlets team-mates very well".
"With that combination I do think he's as ready as we can get him to be at this stage".
USA bars entry to ICC members probing 'war crimes' in Afghanistan
Secretary of State Mike Pompeo speaks during a news conference at the State Department, Friday, March 15, 2019 in Washington. The International Criminal Court is supported by 123 nations, including Switzerland.
"To say that was not his best performance, I know he'd agree with that", said Schmidt.
The Ireland Under 20's can claim Grand Slam glory this evening.
Wales are aiming to win their third Grand Slam under Gatland in what will be his 50th match in charge.
Kearney and O'Brien therefore keep the Leinster contingent in the Ireland XV at seven, with just over two weeks to go before their Heineken Champions Cup quarter-final against Ulster at the Aviva Stadium on March 30.
Replacements: N Scannell, D Kilcoyne, A Porter, Q Roux, J Conan, K Marmion, J Carty, J Larmour.