This study aimed to determine the effectiveness of mastery learning strategy on general mathematics performance of Grade 11 Science, Technology, Engineering and Mathematics (STEM) Students of Boracay National High School in the District of Malay during the School Year 2023- 2024. The pretest-posttest control group design using match paired subjects were utilized in this study. Twenty students were involved in this study where 10 students per group comprised the experimental and control groups. The control group was taught using the traditional way of teaching while the application of mastery learning strategy were used in the experimental group. The statistical tools used were the frequency, sum, percentage, mean and standard deviation for descriptive statistics, t- test for dependent samples, t- test for independent samples and Cohen’s D for inferential statistics. Findings revealed that there was an improvement in the mean score of the control group but remains in the proficient level and those students taught with MLS got a higher mean score that made them to attain the high proficient level. There was a significant difference between the level of general mathematics performance of students.