Introduction: Odontogenic infections are mixed aerobic-anaerobic microbial flora. Infections caused by anaerobic bacteria are serious and life-threatening. The microbial specificity in odontogenic infections is technique sensitive depending on the sampling and culturing of specimens. Materials and Methods: A prospective study was carried out on 100 consecutive cases of odontogenic infections treated at our institute over a period of 5 years by surgical intervention and intravenous antibiotics. This study evaluates the pathogenic potential and virulence factors of aerobes and anaerobes as well as its synergistic interrelations with other infectious flora, by culturing of specimens and testing antibiotic sensitivity in standard microbiological methodology in correlation with patient demographic factors. Results: Of the 100 patients of odontogenic space infection, males were more affected, between third and fourth decades. Caries is the most common etiology with involvement of mandibular molars. Submandibular and buccal space is commonly involved. The most common microorganisms isolated being Staphylococcus aureus and Streptococcus viridans are facultative anaerobes which belong to aerobes and Peptostreptococcus predominated among obligate anaerobes. The empirical antibiotic regimen followed is amoxicillin plus clavulanic acid with Metronidazole, followed by surgical treatment. Clindamycin was preferred as the second line of choice in patients resistance to penicillin drugs with comparable efficacy in it. Conclusion: Our study expanded the knowledge base of the microbial flora associated with odontogenic infections, with special reference to anaerobes. Successful management of odontogenic space infection lies in decompression, removal of etiological factors, and also in selecting appropriate antimicrobial therapy depending on microbial flora isolated, for recovery of patients and preventing complications associated with fascial space infection.