He graduated from the University of Toronto in 1933 and joined its staff two years later after studying at the London School of Economics where he graduated with an M.Sc. in Economics. In 1955 he was awarded the London D.Sc. (Economics) affirmed by the London School of Economics. However, and in accordance with tradition at this time, a Ph. D. in the social sciences was uncommon, and instead he took the normal route of submitting a collection of published papers (16 in all) some twenty years after completing his graduate work. This collection was the 1953 edition of his book, Democracy in Alberta; the theory and practice of a quasi-party system. This claim is supported by the copy of the text held at the London School of Economics which is inscribed "Description: 16pts" as well as the note that "This thesis is the property of the University of London and may not be removed from the Library." The following year he would became a Professor of Political Economy at the University of Toronto in 1956.
He would take several sabbaticals on fellowships which were often spent at English universities including an Overseas Fellowship of Churchill College, Cambridge.
The Canadian Political Science Association presents an annual C. B. Macpherson Prize for the best book on political theory written by a Canadian.
In 1976, when Macpherson was being criticized from both those on the left and the right, he summarised his own life's work in response. Macpherson claimed that what he had always been trying to do was to "work out a revision of liberal-democratic theory, a revision that clearly owed a great deal to Marx, in the hope of making that theory more democratic while rescuing that valuable part of the liberal tradition which is submerged when liberalism is identified as synonymous with capitalist market relations." In the 1980s and the rise of the New Right-inspired governments, which challenged and undermined the mixed economy and welfare state, democratic socialism has seemed to be in retreat. 
Macpherson's best-known contribution to political philosophy is the theory of "possessive individualism", in which an individual is conceived as the sole proprietor of his or her skills and owes nothing to society for them. These skills (and those of others) are a commodity to be bought and sold on the open market, and in such a society is demonstrated a selfish and unending thirst for consumption which are considered the crucial core of human nature. Macpherson spent most of his career battling these premises, but perhaps the greatest single exposition of this view can be found in The Political Theory of Possessive Individualism, where Macpherson examines the function of this particular kind of individualism in Hobbes, Harrington and Locke (and several writers in between) and its resulting pervasiveness throughout most liberal literature of the period. An avowed socialist, he believed that this culture of possessive individualism prevented individuals from developing their powers of rationality, moral judgment, contemplation and even friendship and love. These were the "truly human powers," Macpherson claimed. 
Essay VII of the Essays in Retrieval was titled "Elegant Tombstones: A Note on Friedman's Freedom," and was a direct challenge to certain assumptions of "freedom" made by Milton Friedman in Capitalism and Freedom. For Macpherson, capitalism was discordant with freedom. Part of the disagreement can be found in the differing interpretations of 'freedom.' For self-described 'classical liberals' like Friedman, freedom is negative and is seen as an absence of constraints or freedom of choice; whereas for Macpherson, and other modern liberals, freedom is positive and is defined as the freedom to develop ones fullest human potential. Friedman shows great disdain for positive freedom and its collective nature and uses the term 'liberal' with derision when referring to socialists, while contesting that he was a true liberal.
Macpherson's criticisms of Friedman rest on three issues: (1) an "error" that tarnishes Friedman's attempt to demonstrate that capitalism organizes the economic activities of society without coercion; (2) the "inadequacy" of his assertion that capitalism is a necessary component of freedom, and that socialism is inconsistent with freedom; and (3) the "fallacy" of his evidence that capitalism is an ethically sound principle of distribution.
I. Macpherson contends that the coercion in capitalism is that one cannot choose not to be a capitalist in a capitalist society. They can, of course, choose to change jobs it they want, but they cannot choose not to work. For the exchange to be truly voluntary "the proviso that is needed is whether to enter into any exchange at all."  The workers need money but cannot barter; therefore, they are coerced into the monetary system. Furthermore, the voluntary nature of the exchange is only evident is cases of perfect competition where each product is the same and there are an infinite number of suppliers. Also, Macpherson took issue with corporations as "individuals" in a capitalist society.
II. For Friedman, economic freedom needed to be protected because it ensured political freedom. In other words, capitalism equals freedom. For proof Friedman cites historical examples that demonstrate where the largest amount of political freedom is found the economic model has been capitalist. In Friedman's words, "history suggests...that capitalism is a necessary condition for political freedom." Macpherson counters that the 19th century examples that Friedman uses actually show that political freedom came first and those who gained this freedom, mainly property owning elites, used this new political freedom for their own best interests which meant to open the doors to unrestrained capitalism. It follows then, that capitalism will only be maintained as long as those who have political freedom deem it worthwhile. As the 19th century progressed and suffrage was expanded, there were corresponding restraints placed upon capitalism which indicates that political freedom and capitalism are at odds with one another. "At any rate", Macpherson contends, this "historical correlation scarcely suggests that capitalism is a necessary condition for political freedom."
Friedman also contended that where socialism links economics with politics, economics cannot act as a check on political power. Macpherson countered that there is little evidence that economics does check political power. In fact, in many cases political power becomes subservient to economic power in the capitalist system. In this regard, socialism allows a better check on economic power toward political power than the converse under capitalism. Macpherson accuses Friedman of supplanting a Communist society for a Socialist one; at the very least Friedman does not differentiate between the two.
III. Milton Friedman believed that if most of the regulatory and welfare activities of Western states were discontinued freedom would be advanced. This is true if one follows the negative sense of freedom, but not so if one follows the positive version of Macpherson. Essentially, Friedman, according to Macpherson, does not factor as sort of "ethical claims of equality" into his demand for freedom (that is, market freedom). According to Macpherson, many of the "classical liberals" of previous centuries, which Friedman claims to represent, would have rejected this idea outright.