The T-cell receptor (TCR) is central to the ligand-dependent activation of T lymphocytes and as such orchestrates both adaptive and pathologic immune processes. However, major questions remain regarding the structure and function of the human TCR. Here, we present cryogenic electron microscopy structures for the unliganded and HLA-bound human TCR-CD3 complex in nanodiscs that provide a native-like lipid environment. The unliganded structures reveal two related conformations that are distinct from its structure in detergent. These new "closed and compacted" conformations afford insights into the interactions between the TCR-CD3 and the membrane, including conserved surface patches that make extensive outer leaflet contact, and suggest novel conformational regulation by glycans. We show that the closed/compacted conformations, not the extended one previously reported in detergent, represent the unliganded resting state for the TCR-CD3 in vivo, underscoring the importance of structural interrogation of membrane proteins in native-like environments. By contrast, the structure of the HLA-bound complex in nanodiscs is in an open and extended conformation, showing that physiologic ligand binding is sufficient to induce substantial conformational change in the TCR-CD3 complex. We use conformation-locking disulfide mutants to show that ectodomain opening is necessary for maximal ligand-dependent TCR-CD3 activation, demonstrating that TCR-intrinsic conformational change is necessary for full TCR-CD3 activation and opening numerous avenues for immunoreceptor engineering.