Huber was appalled at the rise of the Nazis. As reports of his country's atrocities in World War II increased, Huber decided that Hitler and his government had to be removed from power. He came into contact with the White Rose movement through some students who attended his lectures: Hans Scholl and Alexander Schmorell. Huber wrote the White Rose's sixth and final leaflet calling for an end to National Socialism.

Huber's political activities came to the attention of the Gestapo and he was arrested on February 27, 1943. By happenstance composer Carl Orff called at Huber’s house the day after he was taken. Huber’s wife begged him to use his influence to help her husband. But Orff told her that if his friendship with Huber was ever discovered he would be “ruined”. Orff left, Huber’s wife never saw him again. Later, wracked by guilt, Orff would write a letter to his late friend Huber imploring him for forgiveness.

Huber was brought before the People's Court on April 19. In a brief show trial, Chief Justice Roland Freisler subjected Huber to a humiliating verbal attack. He was sentenced to death for insurrection.

On July 13, Huber was executed by guillotine at the prison in Munich - Stadelheim Prison, along with Alexander Schmorell. The university had stripped Huber of his position and his doctorate at the time of his arrest.

Attempts to take up a collection for Huber's widow Clara only brought about more trouble and eventually led to Hans Leipelt's arrest and execution.

The square opposite from the main building of the Ludwig Maximilians University of Munich was named "Professor Huber Platz" in his remembrance.

Huber is also known for a biography of Gottfried Leibniz which he completed while in prison.