HMC students must complete the requirements for either a departmental major, an interdisciplinary major, an approved individual program of studies (IPS) or an off-campus major (OCM), and technical minor with approval from the Associate Dean for Academic Affairs. The departmental majors offered are: biology, chemistry, computer science, engineering, mathematics, physics. Interdisciplinary majors offered are: chemistry and biology, mathematical biology, and computer science and mathematics. Requirements for each major are listed in that major's section of the HMC Catalogue.

Every student should seek early guidance from faculty advisors in order to clarify the preparation required for specific majors. Typically, students either select a major or file a tentative IPS plan by the end of the fourth semester.

In the junior and senior years, students take two or three courses each semester in their major and related fields. Some of these are requirements while others are electives. All majors culminate in original research and design opportunities.