Connacht’s Finlay Bealham will start in place of Furlong at tighthead in Cardiff, with Tom O’Toole providing cover from the bench.
Leinster man Furlong has been sidelined by ankle and calf issues in recent weeks but is progressing well and expected back fit within the next seven days.
Andy Farrell’s maiden selection of the tournament contains no further surprises as his side seek to build on a stellar 2022 which propelled them to the top of the world rankings.
Centre Stuart McCloskey will make his first appearance in the championship since his Test debut seven years ago.
The Ulster player has retained the number 12 jersey ahead of Bundee Aki to continue his midfield partnership with Garry Ringrose, having impressed in November’s victories over South Africa, Fiji and Australia.
His only previous appearance in the tournament came in 2016 when he won the first of his nine caps to date in a 21-10 loss to England at Twickenham.
Sexton will be partnered by Leinster team-mate Jamison Gibson-Park in the half-back positions, with Mack Hansen on the right wing and Hugo Keenan at full-back.
Munster lock Tadhg Beirne has been given the nod over fit-again Iain Henderson in a fairly settled forward pack and will line up alongside vice-captain James Ryan.
Ross Byrne has been preferred to rookie Jack Crowley as back-up for number 10 Sexton.
He is joined on the bench by Aki, who was suspended for Ireland’s first two matches in November and has not played since December 23 due to being dropped by Connacht, O’Toole, Henderson, Rob Herring, Cian Healy, Jack Conan and Conor Murray.
Ireland head to Cardiff from their pre-tournament camp in Portugal as marginal title favourites ahead of 2022 Grand Slam winners France.
The Irish have not won a Six Nations match at the Principality Stadium since 2013 and suffered an agonising 21-16 loss there in their opening fixture of the 2021 championship.