Chimeric antigen receptor-modified T cell (CART) therapy has heralded a revolution in cancer immunotherapy. Yet, understanding the qualities that govern effects on in vivo function of CART infusion products (IP) has been challenging. RNA sequencing (RNA-seq), albeit high dimensional in scope, is limited by the dynamic nature of transcription, especially in T cells and CARTs where activation may hinder identification of transiently or minimally expressed genes. We investigated whether epigenomic analyses of histone 3 lysine methylation marks (H3Kme) might uncover genes associated with the potential of starting T cell subsets and CART IP that could not be identified by RNA-seq. We used Cleavage Under Targets and Restriction Using Nuclease (CUT&RUN) to assess whole genome transcriptionally permissive H3K4me2 and repressive H3K27me3 marks in naïve (N), central memory (CM) and effector memory (EM) CD8+ T cells and in CARTs of different potencies and manufactured from different sources. We identify, for the first time, epigenetic predictors of CART cell expansion in a clinical trial (NCT01865617).