The Vice Chancellor is responsible for the academic, administrative and financial affairs of the University; and in the absence of the Chancellor presides over ceremonial assemblies of the University and confers degrees and other academic titles and distinctions of the University.

The Vice Chancellor is elected by the Council on the recommendation of Senate and, once elected, sits as an ex officio member of the board and of all its standing committees except the Audit Committee. Pursuant to university bylaws, the Vice Chancellor is a member of every faculty and every separate academic unit of the university.

There are two Deputy Vice-Chancellors (DVCs); the First Deputy Vice-Chancellor is in charge of the Academic Affairs of the University, while the Second Deputy Vice-Chancellor is in charge of Finance and Administration.

The DVC for Academic Affairs is responsible for the academic affairs of the university. As such, they oversee programmes and policies that promote academic excellence in the University; ensure quality of academic programmes; oversee proper planning and coordination of undergraduate and postgraduate academic programmes; coordinate curriculum development; and ensure optimal utilization of teaching, research and library facilities. The DVC Academic Affairs monitors the Colleges/Faculties/Institutes/Schools, the graduate School, the University Library and the Department of the Academic Registrar.

The DVC for Finance and Administration oversees the finances and administration of the University. In this respect, they are responsible for the planning, budgeting and development of the university; Resource mobilization; Investment; Human resource management; Security; Estates and works; and Procurement. Accordingly, the second DVC monitors the Finance Department, the Planning and Development Department,  and the Security Department, among others.

The University Secretary is charged with the general administration of the University. As such, his office is concerned with policy formulation as well as policy direction, implementation and decision-making. Specifically, the Office administers over; Finance, University plant, Planning and Institutional development, University Service Units, Council matters, Secretarial Services to Council and Human resources. Some of the sections under the University Secretary’s Office include the Legal Unit, the Projects Implementation Unit and the Procurement and Disposal Unit.

The Office of the Director Human Resources oversees the Directorate of Human Resources, which is in charge of personnel activity, such as employment, benefits and staff training and development. Sections under the Directorate include Administration and Personnel, Labour and Welfare, and Appointments Board

The Academic Registrar is the chief coordinator of all matters pertaining to the academic organisation of the University: examinations, research, postgraduate studies, syllabuses and is always the Secretary to Senate and its committees. The Academic Registry oversees admissions & records, examinations as well as staff development and ceremonies.

The University Librarian is the overall head of Makerere University Library Services, which comprise of the Main Library and seven specialised Branch Libraries. Five of these are located at the Makerere University main campus (namely: Education Library, Veterinary Medicine Library, I.A.C.E. Library, MISR Library and EASLIS Library) and two off campus (namely: Albert Cook Library at the College of Health Sciences in Mulago; and MUARIK Library at the Agricultural Institute in Kabanyolo). At the centre of the University is the Main Library, situated on Makerere Hill, opposite the Faculty of Agriculture.

The University Bursar is the manager of financial transactions in the University. This office is responsible for the maintenance of all financial records in the department and a proper accounting system for the University.

The Dean of Students coordinates the activities of student accomodation and is responsible for the welfare and discipline of students in the University. Apart from the Halls of Residence, each of which is governed by a Warden, other sections overseen by the Dean's office include sports and recreation, chapels and mosques, students’ guild and the the counselling centre.

The Office of the Director of Planning and Development Department Makerere University is responsible for planning for the University.To coordinate planning in the University and offer support to strategic and operational decision making in the University through collection, analysis and interpretation of institutional and externally sourced data.

The Director Quality Assurance provides an oversight role to the Directorate, so as to ensure efficiency and effectiveness in university activities. As part of continuous quality improvement, the Directorate undertakes a periodic critical self-assessment of the university in terms of core activities like; teaching, research and community services.