Purpose: To investigate the natural clinical course of more than 5 years and the risk factors of progression in patients with pre-perimetric open angle glaucoma (OAG) of “young age of onset (under age 40)” without treatment. Design: Retrospective observational case series. Methods: Optic disc photography, red-free retinal nerve fiber layer (RNFL) photography, optical coherence tomography, and visual field (VF) examinations were performed every 6 months. Glaucoma progression was defined as structural or functional deterioration. A linear mixed-effects model was used to estimate the rate of structural and functional changes. Kaplan-Meier survival analysis and log-rank testing were used to compare survival experiences, and Cox proportional hazards modeling was performed to identify risk factors for glaucoma progression. Results: Of the 98 eyes of 98 patients (mean age, 30.6 years old), glaucoma progression was detected in 42 eyes (42.9%). The rate of average RNFL thickness thinning was −0.46 ± 0.50 μm/y, and the mean deviation (MD) change was −0.03 ± 0.13 dB/y. The glaucoma progression probability at 5 years was 39% by structural criteria and 5% by functional criteria. Older age at diagnosis (P = .004), presence of temporal raphe sign (horizontal straight line on macular ganglion cell-inner plexiform layer thickness map) (P = .011), lamina pore visibility (P = .034), and greater pattern standard deviation (P = .005) were significant factors for glaucoma progression. Conclusions: In untreated pre-perimetric OAG patients with a “young age of onset” condition, the estimated MD slope for the disease course of more than 5 years was −0.03 dB/y, and the average RNFL thinning rate was −0.46 μm/y. The predictors for progression were structural parameters of temporal raphe sign, lamina pore visibility, and functional parameter of pattern standard deviation.