Background: Ethambutol is a cornerstone drug in first-line antitubercular therapy but is associated with optic neuropathy, which can lead to irreversible visual loss if not detected early. Conventional clinical examinations often fail to detect early or subclinical optic nerve damage. Objective: To evaluate the role of spectral-domain optical coherence tomography (SD-OCT) in detecting early structural optic nerve changes in newly diagnosed tuberculosis patients receiving ethambutol therapy and to correlate these changes with functional visual parameters. Materials and Methods: This hospital-based prospective observational study was conducted at Santosh Medical College and Hospital, Ghaziabad, between 2024 and 2026. Ninety-one newly diagnosed tuberculosis patients (182 eyes) aged ≥18 years, receiving ethambutol as part of first-line antitubercular therapy, were enrolled. Comprehensive ophthalmic evaluation and SD-OCT-based retinal nerve fiber layer (RNFL) analysis were performed at baseline and at 2, 4, and 6 months. Functional assessments included best-corrected visual acuity (BCVA), color vision, and automated visual fields. Statistical analysis was performed using Stata MP-17. Results: Progressive RNFL thinning was observed with increasing duration of ethambutol therapy, becoming significant after 3–4 months and pronounced at 6 months (mean RNFL loss: RE 6.6 ± 3.2 µm; LE 6.7 ± 3.4 µm; p < 0.001). Inferior and temporal quadrants were most frequently affected. Structural RNFL loss correlated strongly with BCVA, color vision defects, and visual field indices. Subclinical toxicity detectable only on OCT ± visual fields was observed in 17% of eyes, while clinical toxicity was seen in 7.7%. Conclusion: SD-OCT is a sensitive, objective, and reliable modality for early detection of ethambutol-induced optic neuropathy. Structural RNFL changes precede functional visual impairment, emphasizing the need for routine OCT monitoring during ethambutol therapy to prevent irreversible visual loss.