Regulatory T cells (Tregs) play crucial roles in both fetal and tumor development. We recently showed that immunosurveillance by pre-existing CD44hiCD62Llow activated/memory Tregs (amTregs) specific for self-antigens protects emergent tumor cells in mice. This Treg response of a memory type is more rapid than and dominates the anti-tumor response of tumor-specific effector T cells. Here, we report striking similarities between the early Treg responses to embryo and tumor implantation. Tregs are (i) rapidly recruited to uterus-draining lymph nodes and activated in the first days after embryo implantation in both syngeneic and allogeneic matings; (ii) they express the markers of the amTreg subset; and (iii) are at least in part self-antigen-specific, as seen in tumor emergence. Unlike in the tumor emergence setting, however, for which pre-immunization against tumor antigens is sufficient for complete tumor eradication even in the presence of Tregs, Treg depletion is additionally required for high frequencies of fetus loss after pre-immunization against paternal tissue antigens. Thus, amTregs play a major role in protecting embryos in both naïve and pre-immune settings. This role and the ensuing therapeutic potential are further highlighted by showing that Treg stimulation, directly by low-dose interleukin-2 or indirectly by Fms-related tyrosine-kinase-3 ligand, lead to normal pregnancy rates in a spontaneous abortion-prone model.