The division was part of the XXII Reserve Corps and was raised through the depots of the elite Prussian Guard, and thus recruited throughout Prussia.
The 43rd Reserve Division initially fought on the Western Front, fighting on the Yser in October–November 1914 and storming Diksmuide in mid-November.
It fought in the Gorlice-Tarnów Offensive, including the 1915 Battle of Lemberg and the assault on Brest-Litovsk.
In June 1916 the division was again sent to the Eastern Front to face the Russian Brusilov Offensive.
Over the course of the war, other changes took place, including the formation of artillery and signals commands and a pioneer battalion.