MHC class Ib genes comprise the majority of the class I family and encode a number of molecules that are expressed at lower levels than class Ia and have limited polymorphism. While much is known about the contribution of MHC Ia at different stages of Mycobacterium tuberculosis (Mtb) infection, our understanding of the diverse group of MHC Ib molecules in host defense against Mtb is quite limited in comparison. We have previously shown that M3 presents several N-formylated Mtb peptides to CD8⁺ cytotoxic T cells during Mtb infection. Using mice that lack MHC Ia/M3 (K^b-/-D^b-/-M3^-/-), we demonstrated that non-M3 MHC Ib-restricted CD8⁺ T cells recognized several Mtb protein antigens, showed polyfunctional capacity, and provided protection against Mtb infection, with Qa-2-restricted CD8⁺ T cells constituting a large proportion of the MHC Ib-restricted CD8⁺ response. Interestingly, we also found that the number of MAIT cells increased significantly during Mtb infection and they comprised a substantial proportion of IL-17-producing T cells in Mtb-infected mice. In addition, we found that Qa-1 could present multiple HLA-E-binding Mtb peptides to CD8⁺ T cells during Mtb infection, and Qa-1^-/- mice were more susceptible to high-dose Mtb infection compared to wild-type controls. The increased susceptibility of Qa-1^-/- mice was associated with dysregulated T cells that were more activated, produced higher levels of pro-inflammatory cytokines, and were more prone to cell death. Thus, our studies demonstrate that MHC Ib molecules participate in the immune response to Mtb infection by presenting diverse Mtb antigens to T cells and modulating anti-Mtb immune responses.