Purpose: Corneal ulcer remains a major, ongoing health issue worldwide as it leads to blindness. The study analyzed the epidemiological patterns, microbiological profiles, antimicrobial resistance, and therapeutic outcomes trends across two time periods to assess changes associated with expanded diagnostic capacity. Methods: A 10-year retrospective research was conducted at Dr. Cipto Mangunkusumo Hospital, Jakarta (2015–2019, 2022– 2024). Clinical, microbiological, and treatment data were analyzed using chi-square tests and multivariable regression with propensity score matching to identify predictors of improvement. Results: A total of 1,100 eyes were examined. About two-thirds of patients were male, and the majority were aged 41 to 60 years, with trauma as the leading risk factor. Diagnostic testing increased markedly after 2022, revealing predominantly bacterial infections, most commonly Pseudomonas aeruginosa and coagulase-negative Staphylococci, with greater culture positivity and organism diversity. Antimicrobial resistance rose substantially, particularly to fluoroquinolones and aminoglycosides, whereas vancomycin (Gram-positive) and ceftazidime (Gram-negative) remained most effective. Clinical outcomes improved significantly in 2022–2024. Chi-square analysis showed ulcer location, size, depth, severity, and anterior chamber reaction were associated with improvement. Multivariable regression identified ulcer size, severity, surgical treatment, and later period as independent predictors of better outcomes, whereas antibiotic class did not independently influence healing. Conclusions Infectious corneal ulcer at our center remains predominantly bacterial, with evolving pathogen profiles and resistance patterns. Improved diagnostic access and standardized therapeutic protocols contributed to better outcomes. Routine culture testing and adherence to local resistance data are essential for guiding empiric therapy.