Antibiotic resistance in ocular infections can affect treatment outcomes. Surveillance data on evolving antibacterial susceptibility patterns inform the treatment of such infections. To assess overall antibiotic resistance profiles and trends among bacterial isolates from ocular sources collected during 10 years. This cross-sectional study of longitudinal data from the ongoing, nationwide, prospective, laboratory-based surveillance study, the Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) study, included clinically relevant isolates of Staphylococcus aureus, coagulase-negative staphylococci (CoNS), Streptococcus pneumoniae, Pseudomonas aeruginosa, and Haemophilus influenzae cultured from patients with ocular infections at US centers from January 1, 2009, to December 31, 2018. Minimum inhibitory concentrations were determined for various combinations of antibiotics and species. Odds ratios (ORs) were determined for concurrent antibiotic resistance; analysis of variance and χ2 tests were used to evaluate resistance rates by patient age and geographic region; Cochran-Armitage tests identified changing antibiotic susceptibility trends over time. A total of 6091 isolates (2189 S aureus, 1765 CoNS, 590 S pneumoniae, 767 P aeruginosa, and 780 H influenzae) from 6091 patients were submitted by 88 sites. Overall, 765 S aureus (34.9%) and 871 CoNS (49.3%) isolates were methicillin resistant and more likely to be concurrently resistant to macrolides (azithromycin: S aureus: OR, 18.34 [95% CI, 13.64-24.67]; CoNS: OR, 4.59 [95% CI, 3.72-5.66]), fluoroquinolones (ciprofloxacin: S aureus: OR, 22.61 [95% CI, 17.96-28.47]; CoNS: OR, 9.73 [95% CI, 7.63-12.40]), and aminoglycosides (tobramycin: S aureus: OR, 18.29 [95% CI, 13.21-25.32]; CoNS: OR, 6.28 [95% CI, 4.61-8.56]) compared with methicillin-susceptible isolates (P < .001 for all). Multidrug resistance was observed among methicillin-resistant S aureus (577 [75.4%]) and CoNS (642 [73.7%]) isolates. Antibiotic resistance among S pneumoniae isolates was highest for azithromycin (214 [36.3%]), whereas P aeruginosa and H influenzae isolates showed low resistance overall. Differences in antibiotic resistance were found among isolates by patient age (S aureus: F = 28.07, P < .001; CoNS: F = 11.46, P < .001) and geographic region (S aureus: F = 8.03, P < .001; CoNS: F = 4.79, P = .003; S pneumoniae: F = 8.14, P < .001; P aeruginosa: F = 4.32, P = .005). Small changes in antibiotic resistance were noted over time (≤2.5% per year), with decreases in resistance to oxacillin/methicillin (oxacillin: -2.16%; 95% CI, -3.91% to -0.41%; P < .001) and other antibiotics among S aureus isolates, a decrease in ciprofloxacin resistance among CoNS (-1.38%; 95% CI, -2.24% to -0.52%; P < .001), and an increase in tobramycin resistance among CoNS (0.71%; 95% CI, -0.29% to 1.71%; P = .03). Besifloxacin retained consistently low minimum inhibitory concentrations. Antibiotic resistance may be prevalent among staphylococcal isolates, particularly among older patients. In this study, a few small differences in antibiotic resistance were observed by geographic region or longitudinally.