In 1661, Louis XIV realised the strategic importance of the town of Breisach am Rhein (Germany) on the banks of the Rhine and decided to make it a base of operations for the French armies across the Rhine. In 1664, while Breisach was still French territory, Sébastien le Prestre, Marquis de Vauban, military architect to Louis XIV, improved, consolidated and strengthened the town, which remained French until the Treaty of Ryswick in 1697, when King Louis XIV returned the stronghold to the Austrian crown (League of Augsburg).
 
Following its loss, in 1698 the King ordered Vauban to find a place to face Breisach. Vauban decided to build a square between Volgelsheim and Wolfgantzen, far enough away to be out of range of Breisach's cannons. On 6 September 1698, the King accepted one of the three scenarios presented, at an estimated overall cost of 4 million pounds, equivalent to the average annual budget for all the kingdom's fortifications at the time. Louis XIV decided on an octagonal plan. Construction began in 1699, using the pink sandstone that is so common in the region. The fortifications were completed in 1702, the stronghold defended in 1703 and operational in 1706, the Saint-Louis church completed in 1736 and the town hall in 1758. Apart from a scare in 1743, the citadel at Neuf-Brisach was never attacked.

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It was besieged for the first time in 1870 during the war against Prussia, following fierce fighting. With more than 6,000 shells falling on the town, Neuf-Brisach was the worst hit of all the Eastern Townships. Having become a German stronghold, more than 75% of the town was rebuilt in less than 5 years, and its plans were substantially modified in 1875. However, because of its fortifications, the town never expanded.
 
Far from the front line of the First World War, Neuf-Brisach, which was German at the time, was spared the fighting. The town became French again in 1918 and regained its strategic position. General Frédéric-Georges Herr, then commander-in-chief of the French artillery in Verdun from 1916 to 1918, who was born in Neuf-Brisach in the house adjacent to that of the Marquisat de Vauban, had the honour of leading the French troops that liberated the fortified town that had seen him born and grow up, and of leading the victorious parade on the rue de Colmar in front of the Marquisat de Vauban in 1918 before conducting a review of the troops on the large parade ground nearby.

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As early as September 1939, Neuf-Brisach was in the operational zone of the Maginot Line, and the entire civilian population was evacuated. Occupied by the Germans from June 1940, the town became a prison camp to which more than 40,000 French soldiers were transferred. In 1945, the ill-informed American army, believing the town to be still occupied, bombed Neuf-Brisach en masse, even though the Germans had already withdrawn. Over 85% of the town was destroyed, while the fortifications remained intact.
 
Today, the town and its ramparts offer a remarkable view of the most accomplished defence system of the 17th century. Vauban's fortifications have been a UNESCO World Heritage Site since 7 July 2008. By decree of 3 November 2023, the town became a Remarkable Heritage Site (SPR).