The molecular mechanisms that underpin acquisition and maintenance of lineage specific gene expression by virus-specific CD8+ T cells are not fully delineated. Post-translational modifications (PTMs) of genome associated histone proteins are a key epigenetic mechanism for regulating gene expression and cellular differentiation. We have utilised a combination of ChIP-seq and in vivo models of influenza virus infection, to map genome wide changes in histone PTM deposition during virus-specific CD8+ T cell differentiation. By examining the location and level of deposition of a combination of H3K4me1, H3K4me2, H3K4me3, H3K27me3, H3K27Ac, chromatin accessibility and binding of the histone acetyltransferase, p300, we have been able to identify both the location and epigenetic signature of known and putative enhancer elements that are differentially marked between naive, effector and memory virus-specific CD8+ T cells. Using this epigenetic blueprint, we were then able to identify two putative transcriptional enhancers located upstream of the Ccl5 gene, a key CD8+ T cell effector gene. These regions where enriched for the transcriptionally permissive H3K4me2, H3K27Ac and interestingly, H3K4me3 modifications in effector and memory, but not naive CD8+ T cells. We were then able to demonstrate that acquisition of Ccl5 transcription upon T cell activation is regulated via temporal and transcription factor (TF) dependent chromatin remodeling involving regulation of several activating and repressive histone modifications within these enhancers. Finally, using the chromatin conformation capture assay (3C) to measure enhancer-promoter interactions, we show that that TF dependent looping of these enhancer elements onto the Ccl5 promoter correlated with transcriptional activation and potential. These studies form a platform for more in depth analysis of key non-coding regulatory elements that regulate acquisition of virus-specific T cell gene expression and maintenance into memory.