Calcium ions (Ca²⁺) function as universal second messengers in eukaryotic cells, including immune cells. Ca²⁺ is crucial for peripheral T-lymphocyte activation and effector functions, and influences thymocyte selection and motility in the developing thymus. However, the role of Ca²⁺ signalling in early T-lymphocyte development is not well understood. Here we show that the inositol triphosphate receptors (IP₃Rs) Ca²⁺ ion channels are required for proliferation, survival and developmental progression of T-lymphocyte precursors. Our studies indicate that signalling via IP₃Rs represses Sox13, an antagonist of the developmentally important transcription factor Tcf-1. In the absence of IP₃R-mediated Ca²⁺ signalling, repression of key Notch transcriptional targets—including Hes1—fail to occur in post β-selection thymocytes, and mice develop aggressive T-cell malignancies that resemble human T-cell acute lymphoblastic leukemia (T-ALL). These data indicate that IP₃R-mediated Ca²⁺ signalling reinforces Tcf-1 activity to both ensure normal development and prevent thymocyte neoplasia.