Genetic screening is an important tool to control, minimize, and prevent genetic disorders. Saudi Arabia started the first national premarital screening (PMS) program to control inherited hemoglobin (Hb) disorders that are the most commonly inherited genetic disorders in the Kingdom of Saudi Arabia. The aim of this study was to assess the knowledge, perception, and attitude among the Saudi population about the PMS program through a questionnaire-based survey. A total of 1,047 candidates were included, divided into three groups. Group A represented the general population, group B was composed of couples presenting for PMS, and group C represented couples who had received their results. There was a fair knowledge among participants of the three groups about the nature of the tests and the targeted disorders, with more than 80% believing that it should include both sexually and genetically transmitted diseases. The concept of genetic counseling was liked by most of the participants. There was a positive attitude toward the program and the majority agreed to apply the PMS program to all couples in all country regions. More than 60% of all the participants were in favor of preventing at-risk marriages.