Background: Early detection of colorectal cancer (CRC) through population-based screening is one of the preventive interventions in areas with a high burden. Its importance is strengthened, given the steady global increase in its age-standardized incidence rate. Aim of Study: To assess the knowledge, attitudes, and practices of adult Saudis attending primary healthcare centers in Buraydah, Saudi Arabia regarding CRC screening. Methods: A descriptive cross-sectional facility-based study was conducted on 517 Saudi adults aged 45 or older attending PHCCs in Buraydah City. Data were collected using the electronic pretested, self-administered questionnaire, which included participants’ sociodemographic characteristics, Personal data relevant to CRC history and screening, Knowledge, Attitude, and Practices about CRC screening. Data were analyzed by the Statistical Package for Social Sciences. Results: This study included 347 males (67.1%), and 382 (73.9%) were <55 years old, while 301 (58.2%) were university-educated. Almost half of the participants (236, 45.6%) heard about screening for CRC. The most agreed upon risk factors for CRC were having a positive family history of CRC (360, 69.6%), alcohol intake (342, 66.2%), smoking (328, 63.4%), colonic polyps (327, 63.2%), and older age (311, 60.2%). The mostly agreed attitude items toward CRC screening were: “Colonoscopy is important for early detection of CRC” (459, 88.8%), “Colonoscopy can help early detection of CRC” (446, 86.3%), “I am not knowledgeable regarding the symptoms and signs of CRC” (433, 83.8%), “Early detected CRC is curable” (428, 82.8%). Only 36 participants (7%) underwent screening for CRC. The main obstacles stated by participants against undergoing CRC screening were: “Lack of the necessary knowledge regarding CRC screening” (393, 76%), “Lack of knowledge about steps of screening for CRC” (51.1%), and “Lack of knowledge about the availability of screening for CRC” (248, 48%). Conclusions: The public’s knowledge about CRC screening in Buraydah City is suboptimal, their attitude is positive, but their practice is poor. The main barriers against CRC screening were their lack of knowledge regarding CRC screening, its steps, and the availability of screening for CRC. Recommendations: To conduct a health education campaign to raise the public’s awareness of CRC and the importance of early diagnosis and management. To overcome the barriers against CRC screening.