It will be his first England appearance since the 2003 World Cup final, and arrives following a solitary comeback game in the Guinness Premiership.
A lacerated kidney meant 12 weeks' sidelined but Andrew, Wilkinson's former Newcastle boss and the current Rugby Football Union elite rugby director, has never doubted his sense of determination.
Andrew said: "I probably know Jonny as well as anyone, and the difficult times he has had over the last three years have been very tough on him.
"It is a travesty the guy hasn't played for England since the World Cup final. He has had dark moments, when he thought he might not get the opportunity again.
"But in the last six to 12 months I have seen a different Jonny. I have seen a Jonny who is going to enjoy the rest of his rugby career, whatever that holds for him.
"I always felt he would come back and, if his body gave him a chance to play, he would go on to become a better player.
"He was only 24 at the World Cup. The work he has been doing over the last two or three years has made him sharper, and he is more experienced as a person.
"He is still only 27. He hasn't even got to the peak of his powers. It is just whether his body will let him play."
New England head coach Brian Ashton has rushed Wilkinson back into business, charged with supervising the world champions' Six Nations title assault following three seasons of abject failure in European rugby's blue riband event.
Wilkinson's presence, plus a Test debut for ex-Great Britain rugby league captain Andy Farrell and Jason Robinson exiting international retirement, guarantees a red-letter day at Twickenham.
Farrell, 31, will line up alongside Wilkinson at inside centre, making an England bow after just seven first-team starts for Saracens since he switched codes in a lucrative move jointly funded by his club and the RFU.
Andrew added: "This is a great opportunity to put Andy Farrell in and have a look.