Background: The objective of this study was to assess the efficacy and safety of faricimab in diabetic macular edema (DME) in patients who were treatment-naïve or previously treated in a real-world setting. Methods: This was a retrospective, observational, single-center study that included 105 eyes from 79 patients diagnosed with DME and treated with intravitreal faricimab between January 2024 and January 2025. Patients were categorized into two groups according to their treatment history, namely treatment-naïve eyes and eyes previously treated (switch group). Functional (best-corrected visual acuity, BCVA) and anatomical (central foveal thickness, CFT; macular volume, MV) outcomes were assessed. The safety of faricimab was evaluated from changes in intraocular pressure and the occurrence of adverse events. Results: BCVA improved significantly in both groups, with a mean gain of +0.16 in treatment-naïve eyes and +0.10 in switch eyes. The mean reduction in CFT was −53.7 µm in the naïve group and −37.8 µm in the switch group. MV decreased by −0.4 mm³ overall, with significant reductions in both groups. No adverse events were reported, confirming the safety of faricimab in routine clinical practice. Conclusions: Faricimab showed significant improvements in functional and anatomical outcomes in patients with DME, regardless of the use of previous anti-VEGF therapies. These findings support the effectiveness and safety of faricimab in a real-world clinical setting and reinforce its potential as a valuable treatment option for DME.