Wilkinson insists he has no qualms about lining up at inside centre, rather than his World Cup-winning position of fly-half, against New Zealand at Jade Stadium on Saturday.
Wilkinson last played Test rugby as an inside centre when a Scott Gibbs-inspired Wales destroyed England's Grand Slam dream at Wembley in 1999.
But Lions chief Sir Clive Woodward has opted for a surprise positional switch, fielding Wilkinson alongside Welsh Grand Slam fly-half Stephen Jones at the expense of Gavin Henson, who misses out completely.
O'Driscoll though, is relishing the prospect of partnering a player he rates among the very best.
"I don't think it affects my game in the slightest," said O'Driscoll, assessing the Lions centre combination.
"I played four years ago with Jonny (at centre) for the Lions against New South Wales, 20 minutes against Wellington last week and we've had all this week in training.
"World-class is world-class, it doesn't matter where Jonny plays. He is just so good at what he does.
"His game is one of the most complete in the world, and I wouldn't totally expect a kicking game from us on Saturday."
For his part, Wilkinson has no issue with Woodward's decision.
"The good thing about the way the game has moved on since that era (1999) is a number 10 on your back really only tells where you stand off set-piece phases," he said.
"Guys now are so skilled at being able to read the game that people pop up all over the place, like second-rows on the end of lines scoring tries. That number on the back doesn't necessarily mean too much once the game gets going.
"The two positions (fly-half and inside centre) tend to work quite well together if you go for that kind of selection.
"There is a slight difference, defensively, but with Neil Back there, and Stephen Jones and Dwayne Peel the way they are in terms of being very committed, enthusiastic and vocal, the change is not a huge one.
"For me, it is an opportunity to go out there and try and put my game into place and try and do the things I like to do from a slightly different position."
Woodward offered a sizeable clue to his intentions by ending the game against Wellington last week with Jones and Wilkinson occupying their respective first Test positions.
And Wilkinson is no stranger to the midfield role, adding: "At the end of my schoolboy career, when England schools toured Australia, I was at 12, and then my first two years at Newcastle I was outside Rob (Andrew) at 12, and the 1998/99 season I played 12 with England.
"I've always enjoyed playing in that position, especially playing alongside people like Rob Andrew and Inga Tuigamala at Newcastle, and Paul Grayson and Mike Catt with England in 1999. It was a real joy to play at 12.
"My recent history over the past five or six years has been more at 10, and I suppose it's having to see things a little bit differently.
"For example, if I was left to wander around on a field, then naturally, I would start drifting into that 10 position, so there is some active thought needed on my part just to make sure that I take into account what I am supposed to be doing at 12 from those phases.
"But once the game gets into play, I've really got to try and make sure I help the guys around me and try and make it a bonus that I am on the field, getting the best out of players outside and inside me."