Born in Frankfurt, Mandel was recruited to the Belgian section of the international Trotskyist movement, the Fourth International, in his youth in Antwerp. His parents, Henri and Rosa Mandel, were Jewish emigres from Poland, the former a member of Rosa Luxemburg's and Karl Liebknecht's Spartacist League. Ernest's start of university study was interrupted when the German occupying forces closed the university.
During World War II, he escaped twice after being arrested in the course of resistance activities, and survived imprisonment in the German concentration camp at Dora. After the war, he became a leader of the Belgian Trotskyists and the youngest member of the Fourth International secretariat, alongside Michel Pablo and others. He gained respect as a prolific journalist with a clear and lively style, as an orthodox Marxist theoretician, and as a talented debater. He wrote for numerous media outlets in the 1940s and 1950s including Het Parool, Le Peuple, l'Observateur and Agence France-Presse. At the height of the Cold War, he publicly defended the merits of Marxism in debate with the social democrat and future Dutch premier Joop den Uyl.
After the 1946 World Congress of the Fourth International, Mandel was elected into the leadership of the International Secretariat of the Fourth International. In line with its policy, he joined the Belgian Socialist Party where he was a leader of a militant socialist tendency, becoming editor of the socialist newspaper La Gauche (and writing for its Flemish sister publication, Links), a member of the economic studies commission of the General Federation of Belgian Labour and an associate of the Belgian syndicalist André Renard. He and his comrades were expelled from the Socialist Party not long after the general strike in 1960-1961 Winter General Strike for opposing its coalition with the Christian Democrats and its acceptance of anti-strike legislation.
He was one of the main initiators of the 1963 reunification between the International Secretariat and the majority of the International Committee of the Fourth International, a public faction led by James Cannon's Socialist Workers Party that had withdrawn from the FI in 1953. The regroupment formed the Reunified Fourth International (also known as the USFI or USec). Until his death in 1995, Mandel remained the most prominent leader and theoretician of both the USFI and of its Belgian section, the Communist League (Belgium).
Until the publication of his massive book Marxist Economic Theory in French in 1962, Mandel's Marxist articles were written mainly under a variety of pseudonyms and his activities as Fourth Internationalist were little known outside the left. After publishing Marxist Economic Theory, Mandel traveled to Cuba and worked closely with Che Guevara on economic planning, after Guevara (who was fluent in French) had read the new book and encouraged Mandel's interventions.
He resumed his university studies and graduated from what is now the École Pratique des Hautes Études in Paris in 1967. Only from 1968 did Mandel become well known as a public figure and Marxist politician, touring student campuses in Europe and America giving talks on socialism, imperialism and revolution.
Although officially barred from West Germany (and several other countries at various times, including the United States, France, Switzerland, and Australia), he gained a PhD from the Free University of Berlin in 1972 (where he taught some months), published as Late Capitalism, and he subsequently gained a lecturer position at the Free University of Brussels. In 1972, his exclusion from the United States was upheld in the US Supreme Court case Kleindienst v. Mandel. In 1978 he delivered the Alfred Marshall Lectures at the University of Cambridge, on the topic of the long waves of capitalist development.
Mandel campaigned on behalf of numerous dissident left-wing intellectuals suffering political repression, championed the cancellation of the third world debt, and in the Mikhail Gorbachev era spearheaded a petition for the rehabilitation of the accused in the Moscow Trials of 1936-38. As a man in his 70s, he travelled to Russia to defend his vision of a free and democratic socialism and continued to support the idea of Revolution in the West until his death.
In total, he published approximately 2,000 articles and around 30 books during his life in German, Dutch, French, English and other languages, which were in turn translated into many more languages. During the Second World War, he was one of the editors of the underground newspaper, Het Vrije Woord. In addition, he also edited or contributed to many books, maintained a voluminous correspondence, and went on speaking engagements worldwide. He considered it his mission to transmit the heritage of classical Marxist thought, deformed by the experience of Stalinism and the Cold War, to a new generation. And to a large extent he did influence a generation of scholars and activists in their understanding of important Marxist concepts. In his writings, perhaps most striking is the tension between creative independent thinking and the desire for a strict adherence to Marxist doctrinal orthodoxy. Due to his commitment to socialist democracy, he has even been characterised as "Luxemburgist".
He is probably remembered most of all for being a tireless rationalist populariser of basic Marxist ideas, for his books on late capitalism and Long-Wave theory, and for his moral-intellectual leadership in the Trotskyist movement. Despite critics claiming that he was 'too soft on Stalinism', Mandel remained a classic rather than a conservative Trotskyist: writing about the Soviet bureaucracy but also why capitalism hadn’t suffered a death agony. His late capitalism was late in the sense of delayed rather than near-death. He still believed though that this system hadn’t overcome its tendency to crises.
Mandel was co-founder, with Livio Maitan, of the International Institute for Research and Education, which was selected as the home of the Ernest Mandel Study Centre after this death. Working together with the Ernest Mandel Foundation, the IIRE plays a key role in expanding the circulation of Mandel's works.