The Leinster centre is facing a spell on the sidelines and will definitely sit out his side's final Six Nations match at Twickenham next Saturday.
Ireland coach Eddie O'Sullivan said: "Brian has a hamstring tear that he picked up in a ruck. It's happened to him before.
"He was in the approach position, his foot slipped and he was hit from behind. It will certainly take him out of the England game.
"We don't have a clue how long he'll be out for. He'll have a scan tomorrow."
The loss of O'Driscoll capped a dismal afternoon for Ireland, who were comprehensively outplayed by a Welsh side that are on the brink of Six Nations glory.
Ospreys winger Shane Williams scored the only try while Stephen Jones and James Hook weighed in with the rest of the points.
Ireland's response was through the kicking of Ronan O'Gara, who slotted four penalties, but they could make no headway with the ball in hand.
Shane Horgan went closest to breaching Wales' line but dropped the ball short as Mike Phillips executed a heroic last-ditch tackle.
O'Sullivan said: "We're disappointed to lose a Six Nations match. It was tight and went down to the wire.
"We started very well and got the dynamics right. We went 6-0 up and had Shane Horgan's try been given we would have been 13-0 up.
"I have no complaints with the decision. It was the TMO's call. For us it wasn't meant to be and Wales bounced back. At 6-3 at half-time they hadn't scored and it was all to play for.
"We rallied well and reeled them in to within a point, but their last penalty killed the game off.
"They were the better team on the day and we didn't get too many line-breaks against them."
Unbeaten Wales sit top of the Six Nations table and victory over France next Saturday will ensure a repeat of their Grand Slam success of 2005.
O'Sullivan added: "Wales are now in the driving seat for the title as they are playing at home.
"They're playing with the same confidence they had in 2005. They're comfortable on the ball and it's very reminiscent of 2005."