The current emplacement of Neudorf used to be a poor spot for urbanisation because of its humidity, although there used to be houses at the North, West and next of the rivers, along with mills.
From the mid-19th century, Neudorf started developing thanks to improvement in water control, notably when the overflow canal for Ill river was built. During the Siege of Strasbourg by the Prussians in 1870, the Northern part of the suburb was flooded when the barrages of Strasbourg were shut closed as to render the terrain difficult to cross and hinder Prussian manoeuvers. This yielded the destruction of several buildings and evacuation of the population
From the late 19th century, the railway that used to run next to Riepberg ditch, currently along Avenue Jean-Jaurès, was moved to the South of the neighbourhood, setting a Southern limit to Neudorf — the former limits have until then been the Krimmeri at the West, and the Ziegelwasser at the East. The new railway was built on an elevation of the fortifications of Strasbourg.
In 1939, the population of Neudorf was evacuated to Dordogne, along with that of the whole of Strasbourg. From the summer of 1940, they were allowed to return to their homes. In 1943, cinema Scala, built in 1938 on Route du Polygone, was turned into a memorial to the 214 killed and 673 wounded in the bombings of 6 September 1943, 17 November 1943 and 1 April 1944. The bombing destroyed 300 buildings, notably a Protestant temple from 1885, and damaged Clinique Sainte-Odile.
With the construction of numerous buildings, Neudorf has again taken an important function in the urban zone of Strasbourg. The most notable are Lycée Jean Monnet (1965), the administrative centre of Strasbourg Eurometropole in 1975, the Southern bypass (1992) and, more recently, urbanisation near Route du Rhin at the North of the neighbourhood, with a cinema and shopping centre.
By 1999, Neudorf was the most populated neighbourhood of Strasbourg, with 39,000 inhabitants.