Saracens centre Nick Tompkins looks set to make his Wales debut after being named on the bench for Saturday's Guinness Six Nations opener against Italy.
Tompkins, who qualifies for Wales through his Wrexham-born grandmother, will provide midfield cover for Hadleigh Parkes and George North, with North moving from the wing to replace injured centre Jonathan Davies.
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But Wales have lost back-row forward Josh Navidi to a hamstring injury, which could also sideline him for games against Ireland and France.
It will be Faletau's 73rd cap, but his first Wales appearance since March 2018.
He has endured a prolonged injury-hit spell in his career, and he missed the World Cup earlier this term because of a collarbone issue.
There is no place in the matchday 23 for uncapped 18-year-old Gloucester wing Louis Rees-Zammit, who has scored 10 tries in 12 games for his club this season.
But scrum-half Rhys Webb is included among the substitutes, with Webb rejoining the Ospreys next term and now being available for Wales selection again following a stint with French club Toulon. He last played for Wales just over two years ago.
Navidi apart, Liam Williams, Owen Watkin, Gareth Davies and Elliot Dee were also unavailable as they continue recoveries from injuries.
Tompkins, 24, played for England Saxons in 2016, but he was not 'captured' by England as their opponents – South Africa A – were not South Africa's recognised second team at the time.
New Zealand-born McNicholl, 29, qualifies for Wales on residency and scored a try during the non-cap game victory over the Barbarians in November. He teams up with back-three colleagues Leigh Halfpenny and Josh Adams.
North, meanwhile, wins his 92nd cap, but Saturday's game at the Principality Stadium will be only the fifth time he has started as a centre for Wales.
Pivac, who takes charge of his first Six Nations game after succeeding Warren Gatland, said: "It is great for Johnny McNicholl to get his first cap. I thought he played really well against the Barbarians.
"George has had a number of games in the midfield for Wales, and more recently for the Ospreys, and he has been running there in training. We have been impressed with him there and he is excited by the opportunity.
"Nick (Tompkins) has trained really well and has impressed, and we are looking forward to seeing him at some stage during the game.
"We've had a couple of injuries.
"Josh Navidi picked up a hamstring injury so he is out for a few weeks, while Liam Williams, Owen Watkin, Gareth Davies and Elliot Dee weren't quite ready to be available for selection.
"The whole team has a great vibe, and we are looking forward to getting out there in front of our home supporters on Saturday."
Wales are defending Six Nations champions and last lost in the tournament almost two years ago when Ireland beat them in Dublin.