North switches to partner Hadleigh Parkes for his fifth start in midfield at international level, with uncapped wing McNicholl coming in for the defending champions' first match of the tournament under head coach Wayne Pivac.
Flanker Navidi looks set to miss the majority of the competition after suffering a hamstring injury.
Fit-again back-row Taulupe Faletau returns for his first international appearance since March 2018, while uncapped centre Nick Tompkins could make his debut off the bench.
Tomos Williams and Dan Biggar made up the half-back pairing at the Principality Stadium, where Josh Adams and Leigh Halfpenny join McNicholl in the back three.
There is no place in the matchday squad for teen flyer Louis Rees-Zammit.
#WALvITA TEAM Johnny McNicholl set for first cap, uncapped Nick Tompkins named on bench for #GuinnessSixNations opener in Cardiff Taulupe Faletau yn dychwelyd i'r tîm am y tro cyntaf ers y Chwe Gwlad 2018. #HWFN
— Welsh Rugby Union (@WelshRugbyUnion) January 30, 2020
Italy will start with Abraham Steyn at number eight in the absence of their most-capped player in Sergio Parisse, who is set to be recalled towards the end of the tournament.
Leonardo Sarto will start at centre for his first appearance since November 2017, while Bristol-born Callum Braley gets the nod at scrum-half.
Alessandro Zanni is set for a 118th cap and will be joined in the second row by uncapped lock Niccolo Cannone, while Danilo Fischetti could make his debut from the bench.
Wales: Leigh Halfpenny, Johnny McNicholl, George North, Hadleigh Parkes, Josh Adams, Dan Biggar, Tomos Williams; Wyn Jones, Ken Owens, Dillon Lewis, Jake Ball, Alun Wyn Jones (captain), Aaron Wainwright, Justin Tipuric, Taulupe Faletau.
Replacements: Ryan Elias, Rob Evans, Leon Brown, Cory Hill, Ross Moriarty, Rhys Webb, Jarrod Evans, Nick Tompkins.
Italy: Matteo Minozzi, Leonardo Sarto, Luca Morisi, Carlo Canna, Mattia Bellini, Tommaso Allan, Callum Braley; Andrea Lovotti, Luca Bigi, Giosue Zilocchi, Alessandro Zanni, Niccolo Cannone, Jake Polledri, Sebastian Negri, Abraham Steyn.
Replacements: Federico Zani, Danilo Fischetti, Marco Riccioni, Dean Budd, Marco Lazzaroni, Giovanni Licata, Guglielmo Palazzani, Jayden Hayward.
Photo Getty Images Caption: Wales flanker Josh Navidi