Investigations about the role of nuclei and nucleation for the inception and formation of cavitation have been part of cavitation research since Harvey et al. (J. Cell. Physiol., vol. 24 (1), 1944, pp. 1-22) postulated the existence of gas filled crevices on surfaces and particles in liquids. In a supersaturated liquid, surface nuclei produce small gas bubbles due to mass transfer of gas or themselves work as weak spots in the liquid that are necessary for a phase change under technically relevant static pressures. Although various theories and models about nuclei and nucleation have found their way into standard literature, there is a lack of experimentally validated theories that describe the process of diffusion-driven nucleation in hydrodynamic cavitation. In order to close this gap we give new theoretical insights into the physics of this nucleation mechanism at technically relevant low supersaturations validated with extensive experimental results. The nucleation rate, the number of produced bubbles per second, is proportional to the supersaturation of the liquid and shows a nonlinear dependence on the shear rate at the surface nucleus. A model for the Strouhal number as dimensionless nucleation rate is derived allowing the estimation of nucleation rates from surface nuclei in hydrodynamic cavitation. The model provides three asymptotes, being a function of Péclet number, Weber number, the supersaturation of the liquid ζ and gas solubility Λ for three different detachment mechanisms, Sr ∝ ζ ΛWe n Pe 1/3 with n = 1/3, 3/4, 1. The theoretical findings are in good agreement with experimental results, leading to a new assessment of the role of diffusion in cavitating flows.