Methods to measure heterogeneity among cells are rapidly transforming our understanding of biology but are currently limited to static measurements of DNA, RNA, and protein abundance. We developed an approach to simultaneously measure biochemical activities and mRNA abundance in single cells to understand the heterogeneity of DNA repair across thousands of human lymphocytes, identifying known and novel cell-type-specific DNA repair phenotypes. Our method provides a general framework for understanding functional heterogeneity among single cells.