Bowe was among the Lions' leading lights during the first half at Suncorp Stadium, breaking from deep on one notable run and almost setting up a try for wing colleague Alex Cuthbert. He also did well to thwart Rod Davies as the Reds hunted for an early try.
However, the Monaghan man damaged his right hand in the opening minutes of the second half and was replaced by his Ireland colleague Jonathan Sexton, with George North and Owen Farrell moving positions in a rejigged back-line.
Bowe had his hand heavily bandaged and his arm put in a sling before returning to the touchline to watch the Lions see out a 10-point win over the Reds.
Speaking at the post-match press conference in Brisbane, Lions head coach Warren Gatland confirmed that the Ireland winger's tour looks to be at an end.
"It doesn't look too good at the moment with Tommy. It looks like he's broken a bone in his hand and the doctors say he'll probably need an operation," he said.
"It's a huge (setback for us). Just the experience Tommy brings, his ability to play on the right wing, left wing, full-back and in the centre.
"We were happy with him on the right wing on Wednesday night and wanted to have a look at him on the left tonight.
"He looked great while he was there and he also slotted into the centre when Manu (Tuilagi) went off. He will be a really big loss."
On Tuilagi's shoulder injury, Gatland added: "Manu is fine. He just got a bit of a 'stinger'. He lost a bit of feeling in his arm, but it is coming back."
There was also positive news for tour captain Sam Warburton as he made a successful return from a knee injury, playing for 74 minutes against Queensland.
Giving his reaction afterwards, the Welsh flanker said: "It's always a bonus to come through injury-free. The medics have done a great job with my knee and I had no problem with it in the game.
"I hadn't played for seven weeks before that so I am pleased to come through and play that long. At the team run yesterday I forgot to get it strapped, that is how good it feels."
An official announcement regarding Bowe's injury and his replacement in the squad is due to be made later today (11.30pm Irish time).