The early history of this school began on 5th January 1973 with the names of Sekolah Menengah Sains Melaka . This also marked the enrolment of 120 pioneer students comprising 80 male and 40 female students . They were placed temporarily in Sekolah Menengah Munshi Abdullah while waiting for the completion of the school building in Ayer Keroh .Due to the delay in the completion , the students had to be transferred to Sekolah Menengah Sains Johor in Kluang the following year .
On 3rd January , 1976 , about 120 more students of Form 1 were again placed in Sekolah Munshi Abdullah , Batu Berendam . However , they managed to be placed in the school in Ayer Keroh when it was completed on 8th May , 1976 . On 10th May 1976 , the school received 160 students to commence their Form Four Education .
Encik Yahya Bin Mayah was elected as the first Principal and Tuan Hj. Sairi Hj. Tahir as the Vice Principal . Both of them were transferred from Sekolah Menengah Munshi Abdullah to this school on 1st May 1976 .
The name Sekolah Menengah Sains Muzaffar Syah Melaka is quite a mouthful . So , we call our school