Chronic, low-level systemic inflammation associated with aging, or inflammaging, is a risk factor for several chronic diseases and mortality. Using data from the Health and Retirement Study, we generated a continuous latent variable for systemic inflammation from seven measured indicators of inflammation and examined associations with another biomarker of biological aging, DNA methylation age acceleration measured by epigenetic clocks, and 4-year mortality (N = 3,113). We found that greater systemic inflammation was positively associated with DNA methylation age acceleration for 10 of the 13 epigenetic clocks, after adjustment for sociodemographics and chronic disease risk factors. The latent variable for systemic inflammation was associated with 4-year mortality independent of DNA methylation age acceleration and was a better predictor of 4-year mortality than any of the epigenetic clocks examined, as well as mortality risk factors, including obesity and multimorbidity. Inflammaging and DNA methylation age acceleration may represent different biological processes contributing to mortality risk. Leveraging multiple measured inflammation markers to capture inflammaging is important for biology of aging research.