<h3>Objectives</h3> The objective was to analyze the available data regarding oral and maxillofacial histoplasmosis (OMH) into a systematic review to integrate the demographic, clinical, and histopathologic features and diagnosis, treatment, recurrence, and survival of this condition. <h3>Study Design</h3> An electronic search without publication date or language restriction was undertaken in November 2020 in the following databases: Medline/PubMed, Web of Science, Scopus, and Embase. The eligibility criteria were restricted to case reports and case series. A descriptive analysis was performed. <h3>Results</h3> One hundred nine articles met the eligibility criteria, yielding 126 cases of OMH. Men (77.8%) were more affected, with a mean age of 50.7 years (SD ± 16.3). In relation to the anatomic site, 54 (42.9%) lesions were found in the tongue, with ulcers (81.7%) being the main fundamental lesion. Most lesions were symptomatic (58.7%) with a unique clinical presentation (57.9%). Oral biopsy was performed in 100% of cases. Regarding laboratory investigations, the anti-HIV test was the most requested exam. Amphotericin B (43.7%) was the treatment choice in the majority of cases. The mean follow-up was 44.8 weeks (SD ± 40). <h3>Conclusions</h3> The present systematic review provides information that could be helpful to clinicians for the diagnosis and management of this condition.