His first major scientific contribution was the application of the concept of dipole moment to the charge distribution in asymmetric molecules in 1912, developing equations relating dipole moments to temperature and dielectric constant. In consequence, the units of molecular dipole moments are termed debyes in his honor. Also in 1912, he extended Albert Einstein's theory of specific heat to lower temperatures by including contributions from low-frequency phonons. See Debye model.
In 1913, he extended Niels Bohr's theory of atomic structure, introducing elliptical orbits, a concept also introduced by Arnold Sommerfeld. In 1914–1915, Debye  calculated the effect of temperature on X-ray diffraction patterns of crystalline solids with Paul Scherrer (the "Debye–Waller factor").
In 1923, together with his assistant Erich Hückel, he developed an improvement of Svante Arrhenius' theory of electrical conductivity in electrolyte solutions. Although an improvement was made to the Debye–Hückel equation in 1926 by Lars Onsager, the theory is still regarded as a major forward step in our understanding of electrolytic solutions. Also in 1923, Debye developed a theory to explain the Compton effect, the shifting of the frequency of X-rays when they interact with electrons.