Objective This study analyzes the clinical characteristics of adult patients with empyema caused by Streptococcus infection, aiming to inform the formulation of diagnostic and treatment strategies as well as prognostic evaluation. Methods A retrospective analysis was conducted on the clinical characteristics of 28 adult patients with empyema confirmed by pleural fluid culture and/or blood culture for Streptococcus at Renmin Hospital of Wuhan University between December 2019 and September 2025. The patients were divided into a group without risk factors (n=8) and a group with risk factors (n=20) based on the presence of comorbidities and/or immunosuppression. The baseline data, clinical manifestations, laboratory and etiological findings, treatment modalities, and clinical outcomes were collected and compared between the two groups. Results A total of 440 patients with empyema were enrolled in this study, among whom empyema caused by Streptococcus infection accounted for 6.4%. CT images of all 28 patients were consistent with the characteristics of pleural effusion, and most patients (19 cases) exhibited loculated effusion accompanied by adjacent pleural thickening. Among them, bilateral empyema was most common (46.43%), followed by right-sided (35.71%) and left-sided (17.86%) empyema. Streptococcus constellatus was the predominant pathogen causing empyema due to Streptococcus infection (50%). Streptococcus intermedius was detected exclusively in the group without risk factors. Other isolated species included Streptococcus anginosus, Streptococcus mitis, Streptococcus pneumoniae, and Streptococcus oralis. No statistically significant differences were observed between the group without risk factors and the group with risk factors in mean age, proportion of patients with fever, or systemic inflammatory markers [white blood cell count, C-reactive protein, procalcitonin (PCT)] (all P>0.05). Five patients in the group without risk factors developed liver function impairment, and the incidence showed a tendency to be higher than that in the group with risk factors (5/8 vs. 3/20 cases, P=0.05). All strains isolated from both groups were susceptible to first-line β-lactam antibiotics, and no significant differences in resistance rates were observed between the two groups (all P>0.05). Regarding clinical outcomes, no significant differences were found in the duration of anti-infective therapy or hospital stay between the two groups. Three patients (3/20, 15.0%) in the group with risk factors died due to empyema and its directly related complications. Among the 28 patients, eight underwent surgical intervention, all of whom improved and were discharged, regardless of risk factor status. Conclusion Streptococcus constellatus is a major pathogen causing adult empyema. Patients without comorbidities and/or immunosuppression have a higher incidence of liver function impairment. In terms of treatment, antimicrobial susceptibility results indicate that first-line β-lactam antibiotics (penicillins/cephalosporins) remain highly effective. However, widespread resistance to clindamycin and other agents warrants attention. For patients with empyema, closed thoracic drainage should be performed as early as possible on the basis of adequate anti-infective therapy.