He started piano lessons at the age of five with his mother, continuing to study with his father, who remained his only teacher. On 19 August 1950, at the age of seven, he gave his first formal concert in his hometown, Buenos Aires.

In 1952, Barenboim's family moved to Israel. Two years later, in the summer of 1954, his parents took him to Salzburg to take part in Igor Markevitch's conducting classes. During that summer he also met and played for Wilhelm Furtwängler. In 1955 Barenboim studied harmony and composition with Nadia Boulanger in Paris. After performing in Buenos Aires, Barenboim made his international debut as a pianist at the age of 10 in 1952 in Vienna and Rome. In 1955 he performed in Paris, in 1956 in London, and in 1957 in New York under the baton of Leopold Stokowski. Regular concert tours of Europe, the United States, South America, Australia and the Far East followed thereafter.

In June 1967, Barenboim and his then-fiancée Jacqueline du Pré gave concerts in Jerusalem, Tel Aviv, Haifa and Beersheba before and during the Six-Day War. His friendship with musicians Itzhak Perlman, Zubin Mehta, and Pinchas Zukerman, and marriage to du Pré led to the 1969 film by Christopher Nupen of their performance of the Schubert "Trout" Quintet.

Following his debut as a conductor with the English Chamber Orchestra in Abbey Road Studios, London, in 1966, Barenboim was invited to conduct by many European and American symphony orchestras. Between 1975 and 1989, he was music director of the Orchestre de Paris, where he conducted much contemporary music.

Barenboim made his opera conducting debut in 1973 with a performance of Mozart's Don Giovanni at the Edinburgh Festival. He made his debut at Bayreuth in 1981, conducting there regularly until 1999. In 1988, he was appointed artistic and musical director of the Opéra Bastille in Paris, scheduled to open in 1990, but was fired in January 1989 by the opera's chairman Pierre Bergé. Barenboim was named music director designate of the Chicago Symphony Orchestra in 1989 and succeeded Sir Georg Solti as its music director in 1991, a post he held until 17 June 2006. He expressed frustration with the need for fund-raising duties in the United States as part of being a music director of an American orchestra.

Since 1992, Barenboim has been music director of the Berlin State Opera and the Staatskapelle Berlin, succeeding in maintaining the independent status of the State Opera. He has tried to maintain the orchestra's traditional sound and style. In autumn 2000 he was made conductor for life of the Staatskapelle Berlin.

On 15 May 2006, Barenboim was named principal guest conductor of La Scala opera house, in Milan, after Riccardo Muti's resignation. He subsequently became music director of La Scala in 2011.

In 2006, Barenboim presented the BBC Reith Lectures, presenting a series of five lectures titled In the Beginning was Sound. The lectures on music were recorded in a range of cities, including London, Chicago, Berlin, and two in Jerusalem.In the autumn of 2006, Barenboim gave the Charles Eliot Norton Lectures at Harvard University, entitling his talk Sound and Thought.

In November 2006, Lorin Maazel submitted Barenboim's name as his nominee to succeed him as the New York Philharmonic's music director. Barenboim said he was flattered but "nothing could be further from my thoughts at the moment than the possibility of returning to the United States for a permanent position", repeating in April 2007 his lack of interest in the New York Philharmonic's music directorship or its newly created principal conductor position. Barenboim made his conducting debut on 28 November 2008 at the Metropolitan Opera in New York for the House's 450th performance of Wagner's Tristan und Isolde.

In 2009, Barenboim conducted the Vienna New Year's Concert of the Vienna Philharmonic for the first time. In his New Year message, he expressed the hope that 2009 would be a year for peace and for human justice in the Middle East. He returned to conduct the 2014 Vienna New Year's Concert, and he is scheduled to conduct the 2022 Vienna New Year's Concert.

In 2014, construction began on the Barenboim–Said Academy in Berlin. A joint project Barenboim developed with Palestinian-American scholar Edward Said, the academy was planned as a site for young music students from the Arab world and Israel to study music and humanities in Berlin. It opened its doors on 8 December 2016. In 2017, the Pierre Boulez Saal opened as the public face of the academy. The elliptical shaped concert hall was designed by Frank Gehry. Acoustician Yasuhisa Toyota created the hall’s sound profile.

In 2015, Barenboim unveiled a new concert grand piano. Designed by Chris Maene with support from Steinway & Sons, the piano features straight parallel strings instead of the conventional diagonally-crossed strings of a modern Steinway.

In 2020, Barenboim curated the digital festival of new music “Distance / Intimacy” with flautist Emmanuel Pahud in the Pierre Boulez Saal. At their invitation ten contemporary composers, among them Jörg Widmann, Olga Neuwirth and Matthias Pintscher, contributed new works engaging artistically with the COVID-19 pandemic. All participating composers and musicians waived their fees, inviting listeners to financially support arts and culture.