Background: Antibiotic (AB) resistance is caused partly by overuse, varies by region, and is influenced by prescriber perspectives. This study sought to determine physicians’ knowledge and attitudes toward AB prescribing, particularly in the Hail region of Saudi Arabia. Methods: An interdisciplinary team created and validated an electronic questionnaire via the test–retest method that measured reliability and consistency. The 19 questions covered the following subjects: demographic information (7), experience with AB resistance in daily work (3), AB prescribing behavior (2), communication with patients regarding AB resistance (3), and prescribing practices (4). The revised questionnaire was prepared and distributed to physicians in the Hail region via multiple electronic communication channels. Inferences were drawn based on descriptive statistics and multivariate regression analysis. Results: The questionnaire responses of 202 participants were eligible for analysis. A total of 70 (34.80%) participants were general practitioners, 78 (38.12%) were engaged in daily work that was only mildly related to AB resistance, and 25 (12.37%) performed work that was substantially related to AB resistance. A total of 88 (43.56%) physicians believed that prescribing behavior contributed to the emergence of AB resistance, whereas 68 (33.66%) did not. Regarding exposure, 51 (25.24%) physicians reported encountering instances of AB resistance monthly, whereas 104 (51.48%) reported seeing cases of AB resistance very rarely. In terms of prescribing practices, 99 (49.0%) physicians prescribed ABs to patients daily and 73 (36.13%) weekly. Regarding AB-resistance-related communication with patients, 73 (36.13%) physicians frequently discussed AB resistance with patients suffering from infections, whereas 13 (6.4%) never discussed it with patients. Conclusion: General practitioners in the Hail region exhibited comprehensive awareness of the elements that contribute to AB resistance but only rarely communicated about the issue with their patients, presuming the latter to be oblivious to the science behind AB resistance. Our findings suggest that the features underlying practitioners’ AB prescribing behavior could be a powerful strategy for lowering AB resistance.