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Existing studies on the item sequenced-performance nexus have produced mixed results. To clarify this contradiction, this study adopted a descriptive research design through a quantitative approach to show how the sequence of items in multiple-choice tests (MCTs) influences the performance of students in Science and Mathematics. Multistage sampling was used to select 370 secondary school students in the Kumasi Metropolis of Ghana. Standardized MCT items in both subjects were adapted from past questions developed by the West African Examination Council. After pilot testing, we arranged test items into three sequences: easy-to-hard, hard-to-easy, and random, based on the difficulty level and administered. A one-way repeated measures ANOVA was performed to check the mean differences in performance after repeated administrations of the tests. The findings revealed that students' performance in both subjects differed significantly depending on the sequence. In both subjects, students performed relatively well in essay-to-hard compared to the random and hard-to-easy sequence. The results highlight that the arrangement of items in MCTs can influence the performance of students in Science and Mathematics related disciplines. Implications and recommendations are discussed. [ABSTRACT FROM AUTHOR]