The research was to ascertain the mediating effect of students' perception in the relationship between the history of mathematics, peer-assisted learning, and students' interest in mathematics. The study was based on 394 students from four selected secondary schools in the Ashanti region of Ghana. The study was a survey, adopting a structured questionnaire as the research instrument. Structural equation modelling was estimated using Amos (v.23) software, to test the hypothesized paths. History of mathematics had no direct effect on students' perception towards mathematics, thereby, students' perception acted as a full mediating variable. Peer-assisted learning had a direct effect on students' perception towards mathematics, thereby, students' perception acted as a partial mediating variable. It is recommended to the Ghana Education Service and the Ministry of Education to inculcate the use of history mathematics, as part of the courses in training mathematics teachers.