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Objectives The study aims to identify the microbiological characteristics, clinical features, and outcomes of adult patients with septic arthritis (SA) at Sultan Qaboos University Hospital (SQUH), Muscat, Oman, over a 10-year period from 2011 to 2020. Methods The study is an observational retrospective study that was conducted by retrospectively reviewing culture-positive SA cases treated at SQUH from 2011 to 2020. The data were collected from the hospital medical record (InterSystems TrakCare®; InterSystems Corporation, Cambridge, MA, USA) for patients whose ages were ≥18 years at the time of admission. The study was approved by the Medical Research and Ethics Committee of the College of Medicine and Health Sciences at SQU. Results A total of 57 adult patients (41 males, 71.9%) were identified to have native joint SA. The median age was 50 years. Among these patients, 24 patients (42%) had pre-existing joint disease, most commonly osteoarthritis (13 cases, 22.8%). Diabetes (23 patients, 40.4%) and sickle cell disease (SCD) (11 patients, 19.3%) were the most common comorbid conditions. A single joint was involved in 49 cases (86.0%). The most involved joints were the knee (34 cases, 59.6%), the hip (seven cases, 12.3%), and the shoulder (five cases, 8.8%). The most common causative pathogens were Staphylococcus aureus in 17 cases (29.8%), followed by Pseudomonas aeruginosa in nine cases (15.8%). Most patients underwent surgical interventions, including arthroscopic washout in 39 cases (68.4%) and arthrotomy in five cases (8.8%). The median duration of intravenous antibiotics was 14 days, and the median duration of oral antibiotics was 14 days. Seven cases were treated with antibiotics only without any surgical intervention. The mortality rate was 7%. Conclusion In this study, SA was more commonly observed among elderly patients and those with comorbidities, particularly diabetes mellitus and SCD. S. aureus was the most common organism.