His father was incarcerated several times in debtors' prison and creditors harassed the family so much that the young Zille was often sent to live with his grandmother.

Zille became best known for his (often funny) drawings, catching the characteristics of people, especially "stereotypes", mainly from Berlin and many of them published in the German weekly satirical newspaper Simplicissimus.

He was the first to portray the desperate social environment of the Berlin Mietskasernen (literally "tenement barracks"), buildings packed with sometimes a dozen persons per room who fled from the rural regions to the expanding industrial metropolis during the Gründerzeit only to find even deeper poverty in the developing proletarian class.

The Berlin "Common People" paid him the greatest respect, and very late in life his fame culminated when both poverty and freedom of expression reached new heights in the roaring twenties, with the National Gallery buying some drawings in 1921, the Academy of the Arts honouring him with a professorship in 1924, and Gerhard Lamprecht making the film Die Verrufenen based on his cartoon characters and stories in 1925.

A museum dedicated to Zille's work opened in Berlin's Nikolaiviertel, in Mitte, in 2002;[2] in 2007 a statue of him by Thorsten Stegmann was erected nearby.

In 1983 director Werner W. Wallroth made an East German film based on a musical written by Dieter Wardetzky and Peter Rabenalt.