A covert opponent of the Nazi regime, he served as a liaison in Zürich between Allen Dulles, station chief for the American OSS, and the German Resistance forces in Germany.

Gisevius joined the secret opposition to Adolf Hitler, began gathering evidence of Nazi crimes (for use in a later prosecution) and attempted to restrain the increasing power of Himmler and the SS.

[3] When the Second World War started, Gisevius joined the German intelligence service, the Abwehr, which was headed by Admiral Wilhelm Canaris, who was secretly an opponent of Hitler.

In 1944, after the failed 20 July assassination attempt against Hitler, Gisevius first hid at the home of his future wife, the Swiss national Gerda Woog, and fled to Switzerland in 1945, making him one of the few conspirators to survive the war.

Peter Hoffmann's biography of Hitler assassination conspirator Claus von Stauffenberg ("Stauffenberg, A Family History," 1992) indicates that after the failure of Stauffenberg's bomb plot in July 1944, Gisevius went into hiding until 23 January 1945, when he escaped to Switzerland by using a passport that had belonged to Carl Deichmann, a brother-in-law of German Count Helmuth James von Moltke, who was a specialist in international law serving in the legal branch of the Foreign Countries Group of the OKW (Oberkommando der Wehrmacht, "Supreme Command of the Armed Forces").

Gisevius wrote in his 1948 book that he considered SS Chief Himmler somewhat of a hypocrite whereas he saw Reinhard Heydrich as one who epitomised Nazi ideals.