In the years immediately after Uganda's independence, Makerere University was a focal point for the literary activity that was central to African nationalist culture.

Many prominent writers, including Nuruddin Farah, Ali Mazrui, David Rubadiri, Okello Oculi, Ngũgĩ wa Thiong'o, John Ruganda, Paul Theroux, Nobel Prize laureate V. S. Naipaul, and Peter Nazareth, were at Makerere University at one point in their writing and academic careers.

[11] The trade school that became Makerere University began operating in 1921 with the first classes in carpentry, building construction and mechanics.

[17] Additional protests, including from parents whose children were left hanging in mid-semester, led to Museveni appointing a special commission to try to rectify the situation but with no promises of reopening.

The institution was granted additional land for expansion into a university by Nsibirwa, a former prime minister of the Buganda Kingdom, in 1945.

On October 7, 2022, a ceremony commemorating the centenary was held at Freedom Square, with Ugandan President Yoweri Museveni in attendance.

A statue monument was unveiled at the entrance of the university's Freedom Square to mark this significant milestone in Uganda's educational sector.

As of September 2015, the halls of residence at Makerere University included the following:[52] In January 2010, the university announced the opening of two new campuses, one in the city of Fort Portal, approximately 310 kilometres (190 mi), by road, west of Kampala, and another one in the city of Jinja, approximately 85 kilometres (53 mi), by road, east of Kampala.

The reconstruction process began in April 2022, starting with tearing down the structurally unsound original building, built in the 1930s and commissioned in 1941.