Sjögren's disease (SjD) is an autoimmune disorder characterized by progressive salivary and lacrimal gland dysfunction, inflammation, and destruction, as well as extraglandular manifestations. SjD is associated with autoreactive B and T cells, but its pathophysiology remains incompletely understood. Abnormalities in regulatory T (T) cells occur in several autoimmune diseases, but their role in SjD is ambiguous. We had previously shown that the function and development of T cells depend on store-operated Ca entry (SOCE), which is mediated by ORAI1 Ca channels and stromal interaction protein 1 (STIM1) and STIM2. Here, we show that mice with a Foxp3 T cell-specific deletion of and develop a phenotype that fulfills all classification criteria of human SjD. Mutant mice have salivary and lacrimal gland inflammation characterized by strong lymphocyte infiltration and transcriptional signatures dominated by T helper 1 (T1) and interferon (IFN) signaling. CD4 T cells from mutant mice are sufficient to induce SjD-like disease in an IFN-γ-dependent manner. Inhibition of IFN signaling with the JAK1/2 inhibitor baricitinib alleviated CD4 T cell-induced SjD in mice. These findings are consistent with the transcriptional profiles of CD4 T cells from patients with SjD, which indicate enhanced T1 but reduced memory T cell function. Together, our study provides evidence for a critical role of dysfunctional T cells and IFN-γ-producing T1 cells in the pathogenesis of SjD.