MHC class I-restricted T cell immunity is essential to control infection with cytomegalovirus (CMV), a clinically important virus that causes significant morbidity and mortality in immunocompromized individuals. Cross-presentation is considered the primary mode of antigen-presentation to generate protective anti-viral CD8(+) T cell immunity. CMV and other herpesviruses (eg Herpes Simplex Virus) encode numerous proteins that interfere with direct antigen presentation, leading to the paradigm that T cell immunity to these pathogens necessitates cross-presentation. However, the antigen presentation requirements needed to generate a protective T cell response to CMV remain unknown. Here, we show that a fully functional anti-viral CD8(+) T cell response can be generated in a system where cross-presentation is shut down by pre-treatment with CpG. Notably, in this setting CD8(+) T cells demonstrate accelerated control of infection, and organ pathology is limited. These data indicate that protective anti-viral T cell immunity to CMV is generated by direct presentation and can be enhanced by pre-treatment with CpG.