Low had Kerem Demirbay and Timo Werner to thank for the historic result with the pair finding the net as the world champions won 3-1 in Sochi.
Demirbay put the Germans ahead and Werner doubled his side's advantage, but Cameroon threatened to mount a comeback when Vincent Aboubakar pulled one back on 78 minutes. However, Werner struck again two minutes later to ensure a comfortable win.
It is the 57-year-old's 100th win in 150 games at the helm of the German team since taking over from Jurgen Klinsmann in 2006.
The win means that Germany, who are chasing their first Confederations Cup trophy, will now face Mexico in the semi-final of the competition after topping Group B.