Purpose: The goal of this study was to investigate the differences in dentists’ knowledge, attitudes, and practice regarding antibiotic use and resistance among two areas of Primorsko-Goranska County (P-GC), Croatia. Materials and Methods: A cross-sectional study based on a structured questionnaire that was given to 230 dental practitioners in outpatient settings of P-GC in 2018. Results: The overall response rate was 68.3% (157/230) and 72.2% (83/115) in the city of Rijeka and 64.3% (74/115) in the rest of P-GC. Dentists from two areas of P-GC held similar knowledge about prescribing antibiotics and attitudes regarding antibiotic use ( p > 0.05). Most of the dental practitioners chose penicillins (65.0% amoxicillin with clavulanic acid and 33.1% amoxicillin) as the first-choice antibiotic in patients with no medical allergies. The trend of prescribing amoxicillin decreases with the age of the dentists ( p = 0.046). Clindamycin (86.6%) was the first choice for patients allergic to penicillin. Postgraduate education changed the attitude toward taking more time to consider whether or not an antibiotic is needed. Croatian dentists had a high awareness of antimicrobial resistance (99.4%). The most common situations for which dentists would prescribe antibiotics were periapical abscess (84.7%), periodontal abscess (72.6%), and implant placement (59.9%). Patient request or expectation (43.4%) and treatment uncertainty (41.5%) were found to be the main factors for prescribing antibiotics with more frequency. Conclusions: Although there is a high level of antimicrobial resistance awareness among dental practitioners, there is still too much overuse of antibiotics and personal responsibility for prudent antibiotic use should be increased. The results of this study indicate that antibiotics are frequently prescribed for indications where surgical treatment should be the first option and the broad spectrum antibiotic is the preferred treatment option.