On March 28, 1945, American units occupied Wiesbaden and moved into their headquarters in the Hotel Rose. The entire area around the Kochbrunnen was declared a restricted military zone. The US Army took command of the city and confiscated numerous houses and the property of the NSDAP and Wehrmacht. The occupation officers followed shortly afterwards. Wiesbaden became the seat of the Military Government (MG) Detachment F1D2 under Commander Colonel James R. Newman. The command center was located at Bierstadter Straße 7.

The Americans initially saw their most important tasks as maintaining public order and initiating the "re-education" and denazification of the population. A strict ban on fraternization was maintained until October 1945. On July 23, 1945, the Mainz suburbs of Amöneburg, Kastel and Kostheim were incorporated into Wiesbaden on American orders.

The most lasting decision of the Americans to date was made on September 19, 1945 with the proclamation of the state of Greater Hesse, consisting of the administrative districts of Wiesbaden, Kassel and Darmstadt, and Wiesbaden as its capital on October 12, 1945.

The headquarters of the American Red Cross, the European Exchange Service, the War Crimes Commission - among others, Hermann Göring was interrogated in the Villa Pagenstecher - and the European Transport System moved to Wiesbaden, and one of three Central Collecting Points in Germany was set up in the museum. The headquarters of the United States Air Force in Europe (USAFE) moved into what is now the Hessian Ministry of Justice in Luisenstraße.

Wiesbaden's new role as one of the most important administrative centers of the Americans throughout Europe resulted in ever more extensive confiscations. The Kurhaus became the Eagle Club, and almost all of the city's hotels were reserved for American soldiers. The Schierstein harbor and parts of it were used by the Rhine River Patrol of the US Navy until 1958.

Americans and Germans worked and lived next door to each other in Wiesbaden, closer together than in any other major German city. This was to become the cornerstone of a particularly close relationship in the future. However, one of the roots of the nascent friendship between nations was the victors' willingness to help the needs of the defeated: in 1945 alone, the Americans distributed over 600,000 tons of food, mostly from surplus army stocks. Thousands of children benefited from American school meals. The first care packages from the USA arrived here in the summer of 1946. Moreover, the Americans were one of the most important employers in the city in the post-war period.

However, the friendship was put to the test by the housing problem: when the Americans marched in, Wiesbaden had 123,000 inhabitants; one year later it already had 198,000. The offices and ministries of the new state of Hesse also needed space, as did the employees and workers of the companies, publishing houses and insurance companies. In 1946, 3,331 apartments in over 700 buildings were requisitioned by the occupying power; by 1948, this figure had risen to almost 6,000. As a result, all non-military institutions had to leave Wiesbaden again - such as the American Red Cross - and the former barracks and properties of the Wehrmacht were increasingly used for military purposes. In 1947, the last "displaced persons" left the Gersdorff barracks in Schiersteiner Straße and the USAFE moved into the so-called Camp Lindsey; the headquarters followed in May 1948. The "Camp Pieri" on the Freudenberg and the hospital on today's Konrad-Adenauer-Ring, both former Wehrmacht facilities, as well as the Erbenheim airfield, now called "Wiesbaden Airbase" or "Y-80", were used intensively.

The number of soldiers stationed in Wiesbaden rose continuously, from 12,000 in 1949 to 16,000 two years later. Closed quarters were created, so-called housing areas, which were initially secured with high barbed wire fences. Nevertheless, the housing problems became increasingly serious. At the same time, it had finally become clear that the Americans would remain in Wiesbaden indefinitely. As a result, a whole series of American hotels and other housing areas were built in the 1950s, such as the American Arms Hotel on Frankfurter Strasse in 1950, the Amelia Earhart Hotel next to the American Hospital in 1955 and the General von Steuben Hotel on Auguste-Viktoria-Strasse in 1956. The Hainerberg Housing Area and the Aukamm Housing Area were opened in 1954. These huge American housing estates, financed by the Germans, made it possible for the Americans to withdraw completely from the city center. In return, the confiscated buildings were mostly released by 1956.

The self-isolation of the occupiers initially had little effect on the close relationship between Germans and Americans in the city. On the contrary, the number of German-American marriages continued to rise and accounted for almost 10% of all marriages between 1955 and 1964. Since 1946, the Americans had made a noticeable effort to establish good neighborly relations. The numerous German-American friendship associations such as Good Neighbors, founded in 1952, or the German-American Women's Club Wiesbaden, founded in 1949 on the initiative of American women, and the German-American Friendship Weeks played an important role in this. The highlight of the German-American friendship was the visit of President John F. Kennedy in 1963.

Even the 1968 movement and criticism of the Vietnam War were comparatively harmless in Wiesbaden, although the Americans felt a stronger headwind. The war in the Far East also had other effects: On the one hand, there was far less money available than before the war for German personnel and for measures to bring Germany and America closer together, and on the other hand, the composition of the troops changed: more and more volunteers were stationed in the city. This had a negative impact on the crime rate, drug consumption and the behavior of the American soldiers as a whole. Added to this was the rapid decline of the dollar since 1970/71. In 1973, the USAFE headquarters were relocated to Ramstein for cost reasons and the airbase in Erbenheim and all other Air Force properties were taken over by the US Army. Of the remaining 21,000 Americans, 15,000 left the city.

When it became known that strong combat units were now to be housed in Wiesbaden, resistance immediately formed on the German side, but this was dispersed by the American military. On March 14, 1976, Brigade 76 was relocated to Wiesbaden. By 1977, fewer than 5,000 Americans, all infantrymen, were stationed in Wiesbaden, living largely isolated from the city's society.

In the 1980s, the existing tensions between Germans and Americans were compounded by the newfound environmental awareness and the peace movement. Overall, the climate between Americans and Germans was characterized by mistrust, particularly due to the terrorist attacks on American military facilities and the increasingly strong anti-war and environmental movement. The low point was certainly 1985, when the American side canceled friendship festivals and the Open House in response to the murder of a soldier by the Red Army Faction in Wiesbaden. Further disputes followed; after the tanks, the dispute flared up over the stationing of combat helicopters and fighter jets in Erbenheim - it was a time of fierce opposition to the deployment of Pershing II missiles in Western Europe. A ruling by the Wiesbaden Administrative Court in 1988 against the stationing of further combat units due to the lack of a corresponding approval procedure added fuel to the fire. On December 14, 1989, the German Bundestag nevertheless approved the deployment of up to 100 aircraft. The fact that this did not happen was due to the fall of the Iron Curtain.

The 1990s brought major troop reductions and the Americans vacated their barracks here ("Camp Pieri" October 1992, "Lindsey Air Station" 1993). Contact between Germans and Americans continued to be kept to a minimum. These tendencies towards isolation were then understandably reinforced by the terrible events of September 11, 2001, even though countless Wiesbadeners expressed their sympathy in many actions.

Since 2005, however, there has been another change in German-American relations: With the relocation of the European headquarters from Heidelberg to Wiesbaden, the city became one of several large, well-equipped main locations of the American army in Europe and Asia. Since autumn 2012, all US Army operations and exercises have been coordinated in Wiesbaden; the city is also home to the headquarters of the 7th Army and the administrative center for all US units in Europe.