Introduction: Antibiotic resistance represents a significant global public health issue, exacerbated by the misuse and overuse of antibiotics. In the fast-paced environment of emergency departments (EDs), the frequent need for empirical antibiotics leads to regular deviations from established guidelines, increasing the risks associated with antibiotic resistance. This study evaluates antibiotic prescribing practices in emergency departments (EDs) and examines how adherence to guidelines impacts clinical outcomes and contributes to reducing antibiotic resistance. Materials and Methods: A retrospective observational analysis was conducted involving 5,000 patient records from January to August 2024 at Esenyurt Necmi Kadıoğlu State Hospital. The data included demographics, clinical presentations, antibiotic usage, laboratory results, and adherence to guidelines. Statistical analyses were performed to assess the associations between prescription practices and patient outcomes. Results: Guideline adherence was observed in 73.08% of cases, significantly reducing treatment duration (p = 0.013). Antibiotic sensitivity testing indicated a sensitivity rate of 74.04%, with patient age significantly impacting antibiotic efficacy (p = 0.024). Logistic regression showed moderate predictive power for complications (accuracy = 51%). Subgroup analysis suggested a borderline association between guideline adherence and outcomes in patients with poor general health (p = 0.081). Conclusion: The findings of this study provide hope in the fight against antibiotic resistance. Adhering to antibiotic guidelines in emergency departments (EDs) not only enhances treatment efficiency and recovery rates but also lays a foundation for future research and policy. The significance of thorough microbiological and clinical evaluations in choosing antibiotics is highlighted, setting the stage for larger studies and the exploration of additional variables. By employing this approach, we can effectively mitigate resistance risks and ensure a brighter future for antibiotic use.