BackgroundCNS actinomycosis is a rare chronic suppurative infection with non-specific clinical features. Diagnosis is difficult due to its similarity to malignancy, nocardiosis and other granulomatous diseases. This systematic review aimed to evaluate the epidemiology, clinical characteristics, diagnostic modalities and treatment outcomes in CNS actinomycosis.MethodsThe major electronic databases (PubMed, Google Scholar, and Scopus) were searched for the literature review by using distinct keywords: "CNS" or "intracranial" or "brain abscess" or "meningitis" OR "spinal" OR "epidural abscess" and "actinomycosis." All cases with CNS actinomycosis reported between January 1988 to March 2022 were included.ResultsA total of 118 cases of CNS disease were included in the final analysis. The mean age of patients was 44 years, and a significant proportion was male (57%).Actinomycosis israeliiwas the most prevalent species (41.5%), followed byActinomyces meyeri(22.6%). Disseminated disease was found in 19.5% of cases. Most commonly involved extra-CNS organs are lung (10.2%) and abdomen (5.1%). Brain abscess (55%) followed by leptomeningeal enhancement (22%) were the most common neuroimaging findings. Culture positivity was found in nearly half of the cases (53.4%). The overall case-fatality rate was 11%. Neurological sequelae were present in 22% of the patients. On multivariate analysis, patients who underwent surgery with antimicrobials had better survival (adjusted OR 0.14, 95% CI 0.04–0.28,pvalue 0.039) compared to those treated with antimicrobials alone.ConclusionCNS actinomycosis carries significant morbidity and mortality despite its indolent nature. Early aggressive surgery, along with prolonged antimicrobial treatment is vital to improve outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13023-023-02744-z.