<p>Sickle cell disease (SCD) is a significant genetic disorder that imposes a considerable global health burden. The notable prevalence of SCD in Tanzania, coupled with extensive economic, psychological, and social ramifications, underscores the importance of premarital genetic screening to carriers of the sickle cell trait. This study aimed to assess the determinants of perception and willingness to uptake premarital genotype screening test for sickle cell disease carriers (PMGS) among health sciences undergraduate students in Dar es Salaam, Tanzania. An analytical cross-sectional design was used among 470 undergraduate students selected using a stratified random sampling technique. A structured questionnaire was used to collect data using Google Forms. Data were analyzed using the Statistical Package for the Social Sciences, version 25. Descriptive and inferential statistical analyses were performed. A total of 448 questionnaires were completed and submitted, with a response rate of 95.3%. More than half of the students (57.24%) had a good perception of PMGS, and the majority (92.2%) expressed their intention to participate in PMGS. Respondents who received information from healthcare professionals had a significant association (<i>p</i> = 0.031) with good perception. Most students were willing to participate in the PMGS program. As healthcare students, they are an important group in the development of national screening programs; similar studies in other universities in Tanzania are needed to obtain representative samples of undergraduates nationwide.</p>