The freshwater polyp Hydra can regenerate from tissue fragments or random cell aggregates. We show that the axis-defining step (“symmetry breaking”) of regeneration requires mechanical inflation-collapse oscillations of the initial cell ball. We present experimental evidence that axis definition is retarded if these oscillations are slowed down mechanically. When biochemical signaling related to axis formation is perturbed, the oscillation phase is extended and axis formation is retarded as well. We suggest that mechanical oscillations play a triggering role in axis definition. We extend earlier reaction-diffusion models for Hydra regrowth by coupling morphogen transport to mechanical stress caused by the oscillations. The modified reaction-diffusion model reproduces well two important experimental observations: 1), the existence of an optimum size for regeneration, and 2), the dependence of the symmetry breaking time on the properties of the mechanical oscillations.