We found that inhaled therapy of tuberculosis (TB) using a Dry Powder Inhalation (DPI) comprising mycobacteriophage D29 and TM4 was non-inferior to oral antituberculosis therapy (ATT) with isoniazid and rifampin in a mouse model of infection with Mycobacterium tuberculosis (Mtb). Mycobacteriophages, natural predators of mycobacteria, are used to treat non-tubercular mycobacterial lung disease (NTMLD), mostly on compassionate grounds. These are administered by mouth, injection or nebulization. With the awareness that DPI deposit more of inhaled medicament deep into the lungs than nebulization, we scaled up preparation and downstream processing of phages, developed DPI formulations, established methods for determining identity, purity, assay, stability, and critical quality attributes (CQA). We carried out cell-based intracellular bactericidal activity assays, pharmacokinetics (PK) and comparative efficacy in Mtb-infected mice. Phage therapy is termed ‘active’ if the patient is dosed with a small number of phages that will amplify by infecting resident bacteria. ‘Passive’ phage therapy aims to flood the patient with enough phages to infect all bacteria present. A high dose (HD, ~10 10 Plaque Forming Units/dose) DPI was non-inferior to human equivalent doses (HED) of oral ATT and non-significantly additive to the bactericidal activity of ATT. A low dose (LD, ~10 6 PFU/dose) DPI was inferior to ATT despite the presence of saturating titers of phages. DPI without concomitant ATT significantly upregulated tumor necrosis factor (TNF) in lung tissue, improved organ morphology, and mitigated histopathology. We conclude that the HD DPI would be a useful adjunct to oral ATT and dose-finding animal studies are required before assessing preclinical safety.