The 25-year-old McLaughlin will start his first international alongside David Wallace and Jamie Heaslip in the Ireland back row.
The in-form Andrew Trimble also returns to the Ireland team for his first start since lining out against England at Twickenham in March 2008 and he is named on the left wing.
Gordon D'Arcy renews his centre partnership with O'Driscoll, while Ronan O'Gara will earn his 94th cap, linking up with his Munster colleague Tomas O'Leary at half-back.
The fit-again Jerry Flannery will start at hooker alongside John Hayes and Cian Healy, while Rory Best has been named in the replacements following his recovery from a neck injury.
Donncha O'Callaghan was forced to pull out of the original starting line-up due to a knee injury. Leinster captain Leo Cullen stepped up to take his place in the second row, with Donnacha Ryan added to the bench.
Jonathan Sexton and Stephen Ferris were not considered for selection, due to dead leg and knee injuries respectively.
Meanwhile, Italy coach Nick Mallett has selected along expected lines for Saturday's clash with Ireland, backing the players that secured a notable win over Samoa in November.
Mallett's selected side is the same as the one that started Italy's 24-6 autumn international win over Samoa, which ended the Azzurri's 13-match winless streak.
Bayonne out-half Craig Gower has recovered from a knee injury to be named at half-back alongside Tito Tebaldi, with the pair boasting just 12 Test caps between them.
Benetton Treviso's Alessandro Zanni will continue at number 8, filling in for injured captain Sergio Parisse who will miss the entire RBS 6 Nations Championship with a cruciate knee ligament injury.
In Parisse's absence, Treviso hooker Leonardo Ghiraldini will captain his country for the second time in his career, while replacement out-half Riccardo Bocchino from Rovigo is the only uncapped player in the visitors' squad.
IRELAND: Rob Kearney (UCD/Leinster); Tommy Bowe (Ospreys), Brian O'Driscoll (UCD/Leinster) (capt), Gordon D'Arcy (Lansdowne/Leinster), Andrew Trimble (Ballymena/Ulster); Ronan O'Gara (Cork Constitution/Munster), Tomas O'Leary (Dolphin/Munster); Cian Healy (Clontarf/Leinster), Jerry Flannery (Shannon/Munster), John Hayes (Bruff/Munster), Leo Cullen (Blackrock College/Leinster), Paul O'Connell (Young Munster/Munster), Kevin McLaughlin (St. Mary's College/Leinster), David Wallace (Garryowen/Munster), Jamie Heaslip (Naas/Leinster).
Replacements: Rory Best (Banbridge/Ulster), Tom Court (Malone/Ulster), Donnacha Ryan (Shannon/Munster), Sean O'Brien (Clontarf/Leinster), Eoin Reddan (Lansdowne/Leinster), Paddy Wallace (Ballymena/Ulster), Keith Earls (Young Munster/Munster).
ITALY: Luke McLean (Benetton Treviso); Kaine Robertson (MPS Viadana), Gonzalo Canale (Clermont Auvergne), Gonzalo Garcia (Benetton Treviso), Mirco Bergamasco (Stade Francais); Craig Gower (Bayonne), Tito Tebaldi (Plusvalore Gran Parma); Salvatore Perugini (Bayonne), Leonardo Ghiraldini (Benetton Treviso) (capt), Martin Castrogiovanni (Leicester Tigers), Carlo Del Fava (MPS Viadana), Quintin Geldenhuys (MPS Viadana), Josh Sole (MPS Viadana), Mauro Bergamasco (Stade Francais), Alessandro Zanni (Benetton Treviso).
Replacements: Fabio Ongaro (Saracens), Matias Aguero (Saracens), Marco Bortolami (Gloucester), Paul Derbyshire (Petrarca Padova), Simon Picone (Benetton Treviso), Riccardo Bocchino (Femi-CZ Rovigo), Andrea Masi (Racing Metro Paris).
Referee: Romain Poite (France)
Assistant Referees: Christophe Berdos (France), Jerome Garces (France)
Television Match Official: Geoff Warren (England)
Match Odds (Paddy Power): Ireland to win: 1/50; Draw: 50/1; Italy to win: 16/1
Pre-Match Quotes: Brian O'Driscoll (Ireland) - "Only having had a fortnight together we've tried to gel as much as we can. We're not expecting fireworks from minute one and trying our most elaborate of plays, we'll work our way into the game and give Italy the respect they deserve and try and grind them down like we would any other side.
"You have to grind teams down for 60, 70, 80 minutes. The difference between winning and losing, and wearing teams down, can be marginal and we're treating this game in the exact same way as any other.
"We are owed nothing in this Six Nations after being unbeaten last year. We have to earn it again and we start from scratch.
"We're not affected by public perception, it's what our own view in the camp is and what we want to achieve ourselves which is important.
"We don't go shouting to the world about what we want to do...but we do want to get better as a team and play a better brand of rugby.
"What makes it such a great competition is that in the eight times I have led my country since 2003, I have always talked about four or five teams capable of winning the Six Nations.
"Look at Scotland, they are the most improved side when you look at the way they beat Australia in November.
"Wales won the Grand Slam the year before us and Italy can take a scalp even if they aren't capable of winning five games on the bounce.
"You don't retain anything, you give it back and try and win it again. That is the way we're looking at it."
Nick Mallett (Italy) - "In recent months, I have pointed to a defined group of players. Those players in the Test matches in November played good rugby, especially against the All Blacks and Samoa.
"Against Samoa, we collected our first ever victory against them. I have called again on that team that won in Ascoli showing great attitude and courage, despite the absence of (injured captain Sergio) Parisse.
"We also retain two players that are important in Marco Bortolami and Andrea Masi, who will start on Saturday from the bench.
"Ireland did not lose throughout 2009. They are the defending champions and a team of the highest level. I expect a similar game with respect to two years ago at Croke Park, which marked my first as coach of Italy.
"We need to put pressure on their scrum, be efficient in touch and in our kicking but above all, not give anything to them on defence for the entire 80 minutes."
Pre-Match Links -
In Pics: Ireland Training At The RDS
Recent Meetings -
2007: RBS 6 Nations: Italy 24 Ireland 51, Stadio Flaminio; Rugby World Cup Warm-Up: Ireland 23 Italy 20, Ravenhill
2008: RBS 6 Nations: Ireland 16 Italy 11, Croke Park
2009: RBS 6 Nations: Italy 9 Ireland 38, Stadio Flaminio