Inside centre Christian Lealiifano was taken off just 54 seconds into his Wallabies debut after picking up a head injury.
Lealiifano was fitted with a neck brace and left the Lang Park field in Brisbane on a stretcher after getting hurt while making a low tackle on Lions centre Jonathan Davies. He was replaced by Pat McCabe, who himself departed in the 47th minute after also picking up a head injury at a ruck.
McCabe was replaced by flanker Liam Gill with Michael Hooper, who started as the openside for the Wallabies, switching to centre.
The Wallabies also lost fullback Berrick Barnes to a similar injury a minute before halftime when he came off worse in a collision with his team mate Israel Folau.
Lions winger George North pushed Folau in the back as the Wallabies winger picked up the ball and crashed into Barnes by the sideline. Barnes also left the field in a neck brace and was replaced by Kurtley Beale.
Lealiifano made a quick recovery and watched the rest of the match from the sidelines. An Australian Rugby Union spokesman said the ACT Brumbies centre wanted to go back on but was kept off as a precaution.
Lealiifano had been due to kick penalties and conversions for the Wallabies.
Barnes was also a goal-kicking option and Beale missed two penalties in the last 10 minutes which could have snatched victory for the Australians.
Wallabies centre Adam Ashley-Cooper was also forced off with a shoulder injury in the closing stages.