The Falcons fly-half has not played since suffering knee ligament damage during a league encounter against Worcester almost two months ago.
Newcastle have not win in the Premiership since but they are boosted by Wilkinson's return and the inclusion of Mat Tait and Toby Flood in the centres.
Tait was not considered for England duty against New Zealand this weekend after suffering a thigh muscle tear.
Flood was overlooked by England head coach Andy Robinson, though he can expect to feature against Argentina at Twickenham next Saturday.
Bristol, without England scrum-half Shaun Perry, hand a debut to New Zealander David Hill barely a week after he arrived in the country.
Hill starts opposite Flood at inside centre and Bristol head coach Richard Hill said: "He's settled in very well. He's very intelligent and has picked up the plays very quickly.
"He's a class act and you can see that already in training. He's got vision and the ability to pass off either hand and the back three will benefit from that."
Wasps travel to Sale with Irish open-side flanker Jonny O'Connor back in the side for the first time since suffering spinal concussion in the Anglo-Welsh Cup seven months ago.
O'Connor comes in for Tom Rees, who is carrying a shoulder injury, and boss Ian McGeechan said: "It's good to have Jonny back and fully recovered for this game.
"We are very lucky with the depth we have in this position - we lose one number seven to injury and we can call on another genuine seven to step in," added McGeechan.
But Wasps have been forced into a major reshuffle after losing Paul Sackey and Mark Van Gisbergen to England.
With Josh Lewsey injured, Jeremy Staunton switches from fly-half to full-back and Edd Thrower makes his first Premiership start since November 2004.
Sale are also much changed after losing five players to England but head coach Kingsley Jones said: "November is a critical month for us as we will be going all out to keep up with the Guinness Premiership pacesetters."
On Saturday, bottom side Worcester travel to Leicester reinforced by the availability of prop Chris Horsman after Premier Rugby refused to release him for Wales duty.
Harlequins, also fighting for their lives at the bottom, host Northampton and London Irish tackle Bath.