Rory Arnold's red card proved costly for the Brumbies as the Lions roared back to earn an ultimately convincing 42-24 Super Rugby win.
The Lions held a slight advantage at the break with Rohan Janse van Rensburg, Robbie Coetzee and Ruan Dreyer cancelling out scores from Tom Banks and Tevita Kuridrani.
But the hosts were staring down the barrel of a fourth straight defeat when Banks' second put the Australian franchise ahead in the 52nd minute in Johannesburg.
However, Arnold – who had been sin-binned in the first half for collapsing the maul – was shown a straight red card for a high tackle on Elton Jantjies.
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A yellow card to Sam Carter shortly after further depleted the Brumbies' numbers, and Marnus Schoeman put the Lions – leaders in the South African conference – back in front with a try from a maul.
Shaun Reynolds then sprinted clear for his first Super Rugby try and another score quickly followed when Jantjies and Ruan Combrinck combined for Lourens Erasmus to dot down.
Full time: Emirates Lions 42 Brumbies 24 #LetsUnite #LIOvBRU pic.twitter.com/LTunEKHj6a
— Emirates Lions (@LionsRugbyCo) May 19, 2018
Earlier, the Sharks overpowered the Chiefs to edge a tight encounter 28-24 at Kings Park.
Robert du Preez, Lwazi Mvovo and Cameron Wright all scored tries for the South African side in a match littered with handling errors.