CD4⁺ T cells play vital roles in controlling systemic infections with the facultative intracellular pathogen Salmonella enterica var Typhimurium (S. Typhimurium). This protective function is related to their provision of IFN-γ, but precisely when and where CD4⁺ T cells supply IFN-γ in vivo remains unresolved. We have utilized adoptive transfer studies and IFN-γ reporter mice to address this issue in the context of primary and secondary Salmonella infections. After immunization with growth attenuated Salmonella, we demonstrated that helper T cell-mediated immunity is present in the spleen at the effector phase of the infection, but this immunity decreases towards clearance of Salmonella. In comparing helper T cell responses between spleen and liver in Salmonella-infected mice, we have observed a previously uncharacterized population of helper T cells that was associated enhanced local control of Salmonella in the liver. These CD4⁺ T cells expressed surface markers and exhibited functional characteristics associated with tissue residence. Specific blockage of ARTC2 enzyme mobilized liver CD69⁺ helper T cells and upon transfer to naïve mice conferred enhanced resistance to lethal Salmonella infection. Taken together these findings identify the liver as a critical site of Th1 CD4⁺ T cell immunity against primary and secondary Salmonella infections.