Background: Low back pain (LBP) is one of the most common health problems. Red flags (RFs) of LBP are risk factors that are reported during clinical assessment to determine serious illness. This study aimed to assess primary health-care physicians’ knowledge of and practices for RFs of LBP and identify variables associated with a high level of knowledge and awareness about it. Methods: An observational cross-sectional survey was conducted in 2021 among a random sample of 261 primary health care (PHC) physicians in the Jazan Region in southwest Saudi Arabia. A web-based questionnaire was used to collect data on LBP red flags awareness and practices. Descriptive (frequency and percentage) and inferential statistics were used for data analysis. Results: The overall mean score of RFs knowledge among physicians was 82.33 ± 36.3, with 95% confidence interval (CI); (77.7– 86.9). Regarding the Physician’s practices, more than 95% of the participants would refer patients to higher levels in the presence of symptoms or signs of RFs. General practitioners and residents were significantly more likely to ask for an Xray, even with symptoms that had persisted for less than 2 weeks without RF signs (p = 0.006). The overall percentage of patients with nonspecific LBP referrals was as high as 57.8%. The number of patients with LBP seen per month (fewer than 15) and female physician were associated with an increased level of knowledge (OR = 2.2, 95%, P < 0.05) and (OR = 2.2, 95%, P < 0.05) respectively. Conclusion: Overall, awareness of RFs for LBP and referring critical patients who present with LBP is good among PHC physicians in the Jazan Region. Junior physicians have a low threshold to request images. The referral rate for nonspecific LBP is still high, which could overwhelm spinal clinics. Further educational programs for back pain management are recommended.