Cardiff Blues openside Williams has taken over the captain's armband for only the seventh time in his career from calf injury victim Ryan Jones for the showdown at Croke Park.
But the veteran flanker, who played alongside Ireland centre O'Driscoll on a trio of British Lions tours in 2001, 2005 and 2009, has lavished praise on the Leinster legend set to notch up a milestone 100th cap.
"Brian is without doubt, the best player in the northern hemisphere in the last decade," said Williams.
"In fact, he's one of the best ever and that includes the Lions, Europe and the world.
"For me, there is nothing he can't do. Sometimes you get players who are good defenders or have good passing skills but Brian has the complete package.
"I can't speak highly enough of him. He's an unbelievable player."
It will be an afternoon of celebration for both captains with Williams also making history by overtaking Colin Charvis as Wales' most-capped forward on 95 international appearances.
The familiarity will not finish there with almost two-thirds of the starting line-ups selected by coaches Declan Kidney and Warren Gatland present on last summer's Lions tour to South Africa.
With players from both countries regularly facing each other in the Magners League as well, the majority of players will be far from strangers.
But despite his closeness to a number of his Irish counterparts, Williams insists it will be business as usual in Dublin.
"We all know each other well through playing in the Magners League and, of course, the majority of us were on tour together in the summer," added Williams.
"Everyone got on brilliantly out in South Africa and it has been well documented how good a tour it was off the field.
"But once the whistle has gone on Saturday, it's largely irrelevant. We have a job to do on the field."
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