Due to the penetration of alternative renewable energies, the stabilization of the electrical power network relies on the off-design operation of turbines and pump-turbines in hydro-power plants. The occurrence of cavitation is however a common phenomenon at such operating conditions, often leading to critical flow instabilities which undercut the grid stabilizing capacity of the power plant. In order to predict and extend the stable operating range of hydraulic machines, a better understanding of the cavitating flows and mainly of the transition between stable and unstable flow regimes is required. In the case of Francis turbines operating at full load, an axisymmetric cavitation vortex rope develops at the runner outlet. The cavity may enter self-oscillation, with violent periodic pressure pulsations. The flow fluctuations lead to dangerous electrical power swings and mechanical vibrations, dictating an inconvenient and costly restriction of the operating range. The present paper reports an extensive numerical and experimental investigation on a reduced scale model of a Francis turbine at full load. For a given operating point, three pressure levels in the draft tube are considered, two of them featuring a stable flow configuration and one of them displaying a self-excited oscillation of the cavitation vortex rope. The velocity field is measured by two-dimensional (2D) particle image velocimetry (PIV) and systematically compared to the results of a simulation based on a homogeneous unsteady Reynolds-averaged Navier–Stokes (URANS) model. The validation of the numerical approach enables a first comprehensive analysis of the flow transition as well as an attempt to explain the onset mechanism.