MLKL and RIPK3 are the core signaling proteins of the inflammatory cell death pathway, necroptosis, which is a known mediator and modifier of human disease. Recently, reports have suggested a novel role for necroptosis in aging, particularly in the male reproductive system. However, whether other age-related phenotypes emerge in necroptosis-deficient mice, remains unknown. Here we present the first comprehensive analysis of age-dependent phenotypes in a cohort of littermate-controlled, Mlkl-/- and Ripk3-/- mice on a congenic C57BL/6J genetic background. We show that genetic deletion of Mlkl, but not Ripk3, in female mice interrupts immune system aging, specifically delaying the age-related reduction of circulating lymphocytes. Mlkl-/- female mice were also protected against age-related, low-grade chronic sterile inflammation, with a reduced number of inflammatory infiltrates present in the connective and muscle tissue at 17 months relative to wild-type littermates. Our observations implicate MLKL in sterile inflammation and immunosenescence, the age-dependent decline in immune function, in mice. We anticipate our study to be a starting point for more in-depth analyses of necroptosis-driven aging in mice and humans. Furthermore, these results will inform ongoing studies into the potential human indications for necroptosis-targeted therapies.