Background Bacterial wound infections are the second leading cause of mortality globally, with approximately 50% of contaminated wounds evolving into chronic infections. In Tanzania, this challenge is exacerbated by the over prescription of antibiotics and the emergence of drug-resistant bacteria, compounded by inadequate hospital hygiene and sanitation practices. This study investigated chronic wound infections in Tanga, Tanzania, focusing on antibiotic susceptibility patterns. Methods A cross-sectional, mixed-methods study was conducted at the Tanga Regional Referral Hospital (TRRH) from July to December 2023. Pus and Culture Sensitivity tests were performed on samples from 89 chronic wound patients to identify bacterial isolates and assess antibiotic susceptibility. Data was analyzed using STATA, Excel, and Python. Results Of 89 patients, 82 (92.1%) had positive bacterial isolates in wound cultures, predominantly with Staphylococcus aureus, 24 (29.3%). Surgical-site infections (SSI) were the most prevalent diagnosis, followed by diabetic foot ulcers and septic wounds. Antibiotic resistance analysis revealed a marked trend in multi-drug resistance (MDR), notably against amoxicillin, while meropenem was identified as the most effective antibiotic. Conclusion The elevated rate of MDR at TRRH, particularly against commonly used antibiotics, emphasizes the need for improved antibiotic stewardship and healthcare worker education. It necessitates increased health awareness about effective wound management and the development of robust healthcare strategies to combat the escalating challenge of MDR.