The 27-year-old made a successful return with UL Bohemians recently and appeared as a second half replacement in Munster's midweek win over Australia.
With Keith Earls recalled to the Ireland squad, Murphy will start at outside centre for Munster in this weekend's clash with the Scarlets. It will be his first Magners League start since injurying his ankle against the Newport Gwent Dragons 14 months ago.
The second and final change to the side that beat the Wallabies 15-6 sees experienced flanker Alan Quinlan return in the back row, at the expense of Peter O'Mahony.
New Zealander Peter Borlase will make his Magners League debut in the front row, while Cork Constitution club-mates Billy Holland and Ian Nagle continue their second row partnership.
Munster currently hold a four-point lead over the Scarlets at the top of the Magners League, but there is a tight turnaround between the Australia game and the visit of the in-form Welsh region.
"It will be difficult, but that is the beauty of rugby," explained Munster head coach Tony McGahan.
"How the group and everyone manages that, to leave Tuesday night where it is, to park up for training on Thursday afternoon, and apply ourselves to a situation where there are four points on board will be important."
Reflecting on that battling victory over Australia, McGahan was full of praise for the coaching staff and players.
"Full credit to Laurie (Fisher) and the work he has done there. I thought our breakdown stuff, on both sides of the ball, and also our defence was well-marshalled and very tight. Anthony Foley has also done a tremendous job with that this season.
"More than anything, I was delighted for the players. It was all about the 22 guys who played the game.
"Their display and the effort they put in was tremendous. I don't know if it surpassed the game with the All Blacks two years ago. But it was a chance to get our own little part of history and our own little place in the museum."
MUNSTER (v Scarlets): Johne Murphy; Doug Howlett, Barry Murphy, Sam Tuitupou, Denis Hurley; Paul Warwick, Duncan Williams; Wian du Preez, Damien Varley, Peter Borlase, Billy Holland, Ian Nagle, Alan Quinlan, Niall Ronan, James Coughlan.
Replacements: Mike Sherry, Dave Ryan, Stephen Archer, Peter O'Mahony, Tommy O'Donnell, Conor Murray, Tom Gleeson, Scott Deasy.