Tissue-resident memory T cells (T RM cells) in the airways mediate protection against respiratory infection. We characterized T RM cells expressing integrin α E (CD103) that reside within the epithelial barrier of human lungs. These cells had specialized profiles of chemokine receptors and adhesion molecules, consistent with their unique localization. Lung T RM cells were poised for rapid responsiveness by constitutive expression of deployment-ready mRNA encoding effector molecules, but they also expressed many inhibitory regulators, suggestive of programmed restraint. A distinct set of transcription factors was active in CD103 + T RM cells, including Notch. Genetic and pharmacological experiments with mice revealed that Notch activity was required for the maintenance of CD103 + T RM cells. We have thus identified specialized programs underlying the residence, persistence, vigilance and tight control of human lung T RM cells.