Discrimination, or unfair treatment of individuals based on social group membership, is a major public health concern. To understand health inequities, it is critical to examine the physiological mechanisms-such as systemic inflammation-through which discrimination impacts health. However, estimations of the discrimination-inflammation association vary widely across studies, and it is unclear if the magnitude of the association varies as a function of methodological and sample characteristics. We conducted a systematic review and meta-analysis of the association between discrimination and inflammation in 47 articles that yielded 161 effects. A series of meta-regressions were conducted using random effects models to estimate the overall effect size and effect sizes among subgroups of different combinations of discrimination measures and inflammatory markers. Results revealed a significant, positive overall association, such that greater discrimination was associated with higher levels of systemic inflammation among ∼74,763 participants ( r = 0.087, p < .001). Subgroup analyses showed that the magnitude of the association varied by the type of discrimination measured, the specific inflammatory marker, and methodological features. Discrimination was significantly associated with CRP and IL-6. There was a significant, positive association between discrimination and inflammation in studies that measured racial/ethnic discrimination specifically. Statistical power is also a significant contributor to our ability to estimate effects between discrimination and inflammation. Overall, the current literature provides evidence that greater discrimination is associated with higher levels of inflammation. We need greater theoretical and methodological precision to advance our understanding of the mechanistic pathways by which discrimination gets under the skin.