Byrne will deputise for injured Leinster team-mate Johnny Sexton in the number 10 jersey to continue his international resurgence, while Casey comes in for fellow Munster man Conor Murray.
The fledgling pair have combined well from the bench in victories over Wales and France in the opening two rounds of the tournament and Farrell expects more of the same at Stadio Olimpico.
“They have earned the right to start,” said Farrell. “And, from what we have seen so far, it’s been a good start to the week.
“Preparation has been great and yeah, they seem ready for it.”
Speaking specifically of Byrne, he continued: “He’s been great. He’s earned the right to run the team and transfer everything that we have seen in training to a performance that’s got authority and takes his team with him.”
Byrne feared his Test career may be over before returning from 20 months in the international wilderness to kick the decisive penalty in Ireland’s autumn win over Australia.
Only two of his previous 16 caps have been won as a starter, while Casey, who made his debut away to Italy two years, has only once before begun a match for his country.
Hooker Ronan Kelleher, lock Iain Henderson, number eight Jack Conan and centre Bundee Aki have also been recalled to face the Azzurri.
Just two of the alterations are enforced, with Sexton and Tadhg Beirne ruled out by injuries sustained in the 32-19 success over the French.
Farrell dismissed the notion he has shaken things up “for the sake of it” and expects his Grand Slam-chasing side to produce their best display of the competition so far.
“We have been together for a good few weeks now, so people are certainly up to speed,” he said.
“People wouldn’t have been selected if they weren’t in the right place.
“We’re not just turning things around for the sake of it, we are turning things around because we think it’s a strong side for us going forward, for this game and for the future as well.
“I don’t think there are that many changes, to be fair.
“The reality is, this is our third game of the competition and we expect it to be our best performance of the competition. That’s how it should be and that’s what we are aiming for.”
James Ryan will skipper Ireland for the seventh time in the absence of influential captain Sexton, while centre Garry Ringrose will win his 50th cap.
Farrell believes his in-form side, who sit top of the world rankings, have a squad packed with leaders.
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“I feel we’re in a great place that we would be more than happy for a handful of players to captain the side,” he said. “James is the lucky one this weekend.
“But Garry Ringrose is an exceptional leader. I’m sure that he’ll be captain of Ireland one day. Peter O’Mahony, Iain Henderson, and more and more of those type of players.
“You look at the development of somebody like Caelan Doris, of Hugo Keenan or Garry, there’s a reason why they’re playing so well, it’s because of how they don’t just lead themselves off the field, they lead others as well.
“They tend to work unbelievably hard off the field and try and give as much as they possibly can to their team-mates so, in that regard, I feel we’re pretty lucky.”