The college was established, built and partially endowed in 1962 by the Massey Foundation and officially opened in 1963, though women were not admitted until 1974.

The college is well-connected with prominent figures of the national establishment, and is the sponsor and host of the annual Massey Lectures.

Of the establishment of a new graduate college, Massey wrote, "It is of great importance that it should, in its form, reflect the life which will go on inside it and should possess certain qualities—dignity, grace, beauty, and warmth.

On July 1, 2014, Hugh Segal, formerly a member of the Senate of Canada, became the fifth head of the college for a seven-year term, but he resigned in 2019.

The commentary from the award’s jury reads as follows: "Massey College is a skillful and humane interpretation of Arts and Crafts sensibilities in a modernist idiom.

It is remarkable for its seamless integration of exterior and interior design, including the rich detailing of its custom furnishings and fittings.

"Recognizing buildings that demonstrate architecture’s beauty, endurance and lasting contribution to the community and to society", a Landmark building "establishes a design excellence standard for future generations, enhances its environment and the public realm, recognizes and respects its surroundings; and contributes to the neighbourhood, the community or the city through its unique identity."

Fall 2013 issue of Perspectives magazine, published by OAA, was dedicated to Ron Thom and featured Massey College.

The chapel was extensively redesigned in 2006 by the College architects, Brigitte Shim and Howard Sutcliffe, and rededicated in June of the following year.

[12] Junior Fellows are postgraduate students "of distinguished ability"[13] at the University of Toronto, either in the study of art and sciences subjects or a professional discipline such as law, engineering, or medicine.

Junior Fellows are elected based on: Junior Fellows of the college have included Bernard Amadei, Roger S. Bagnall, Claire Battershill, Andrew Battershill, Dawn R. Bazely, Anne Bayefsky, Warren Cariou, Yeon-Koo Che, Phil De Luna, Eve Egoyan, Carol Hansell, Alister Henskens, Tajja Isen, Padriac Kenney, Vladimir J. Konečni, Catherine Manoukian, Brian McGing, Sharon Moalem, Jacqueline Murray, Chika Stacy Oriuwa, Julie Payette, K. K. Seet, Joseph Tabbi, Vahid Tarokh, Donna Vakalis, Diana Valencia, Douglas N. Walton, Michael Wex, and Oliver Whitehead.

Journalism Fellows are distinguished mid-career Canadian and international journalists who are selected annually by a special committee that includes the president of the University of Toronto, the head of Massey College, and other members appointed by them.

Notable Senior Fellows and Senior Residents of the college have included Haroon Siddiqui, John Polanyi, Ursula Franklin, Mikhail Baryshnikov, Margaret Atwood, Sir Christopher Ondaatje, James Orbinski, Peter H. Russell, Janice Stein, Michael Ignatieff, Adrienne Clarkson, Beverley McLachlin, Hal Jackman, John Ralston Saul, Michael Bliss, Anthony Pawson, Julie Payette, Chantal Hébert, Sir Graham Watson, Rosalie Abella, Bob Rae and Zainub Verjee.

In conjunction with the University of Toronto's School of Graduate Studies, Massey fellows organize an annual symposium of interest to the broader community.

It convenes monthly during the school term and serves as a discussion forum for topics related to medicine, the health sciences, and issues of interest to students.

The college also strives to preserve an Oxbridge-type atmosphere by mandating the wearing of gowns at dinner, and incorporating regular High Tables—into its schedule; and balances this with very active outreach programs [citation needed].

Massey College also hosts its own Junior Fellow Lecture Series, sometimes called WIDEN-Massey, where graduate student members of the community are invited to talk about their research in a general way to their non-specialist peers.

The Clarkson Laureateships in Public Service are the highest honour the College awards annually to members of its community.

[15] Over the years, notable philanthropists, academics, community organizers, politicians, and activists have been awarded a Clarkson Laureateship, including Ursula Franklin, William Davis, and Mary Eberts.

[16] The Laureateships are usually awarded at the first High Table in January in the presence of the Laureates’ families and Massey College peers.

It is tradition for the Laureates to donate the monetary component of the award to a charitable cause of their choosing, often detailed in their acceptance speech.