He was born in Oranienburg, Germany (near Berlin) and studied physics at the University of Berlin under Max Planck. During World War I he was taken prisoner by the Russians and spent 5 years in captivity in Siberia.
After the war, he collaborated with Hans Geiger at Physikalisch-Technische Reichsanstalt in Berlin, where he made his most important discoveries. He discovered that if a single particle is detected by two or more Geiger counters, the detection will be practically coincident in time. Using this observation he constructed the coincidence circuit allowing several counters in coincidence to determine the angular momentum of a particle. He studied the Compton effect using such a set up and establishing the modern analysis of scatter processes.
During the 1920s Bothe used the coincidence method to discovery penetrating radition coming from the upper atmosphere now known as cosmic rays. His data indicated that the radition was not composed exclusively of gamma rays, but was also composed of high energy particles (now known to be mostly mesons). Bothe began applying the coincidence method to the transmutation of light elements by the bombardment with alpha particles in 1927. In 1930 he found that the radiation emitted by beryllium when it is bombarded with alpha particles a new form of penetrating high energy radiation, which was later shown by James Chadwick to be neutrons.
In the 1930s Bothe started working at the Kaiser Wilhelm Institute (now the Max Planck Institute) and in 1938 Wolfgang Gentner and Bothe published the energy dependence of the nuclear photo-effect, which ws the first decisive evidence that absorption spectra of nuclei are accumulative and continuous. In 1943 he completed Germany's first cyclotron.