Homeostasis of the immune system depends on the proper function of regulatory T cells (Tregcells). Compromised suppressive activity of Tregcells leads to autoimmune disease and graft rejection and promotes anti-tumor immunity. Here we report a previously unrecognized requirement for the serine-threonine phosphatase PP2A in the function of Tregcells. Tregcells exhibited high PP2A activity, and Tregcell–specific ablation of the PP2A complex resulted in a severe, multi-organ, lymphoproliferative autoimmune disorder. Mass spectrometry revealed that PP2A associated with components of the mTOR metabolic-checkpoint kinase pathway and suppressed the activity of the mTORC1 complex. In the absence of PP2A, Tregcells altered their metabolic and cytokine profile and were unable to suppress effector immune responses. Therefore, PP2A is required for the function of Tregcells and the prevention of autoimmunity.