Lupu was born in Galaţi, the son of Meyer Lupu and Ana Gabor. He began piano as a 6-year old (with Lia Busuioceanu), making his public debut at age 12, in a concert featuring his own compositions. After completing high school in Galaţi, and graduating from the Popular School for the Arts in Braşov, Lupu continued his studies at the Bucharest Conservatory with Florica Musicescu (who also taught Dinu Lipatti), and Cella Delavrancea. In 1961, he was awarded a scholarship to the Moscow P.I. Tchaikovsky State Conservatory, where he studied with Galina Eghyazarova, Heinrich Neuhaus (who also taught Sviatoslav Richter and Emil Gilels), and Stanislav Neuhaus.
He currently resides in Lausanne, Switzerland.
Lupu's concert appearances and recordings for Decca, though not frequent, consisting of a limited repertoire, have been consistently acclaimed. Although trained in the Russian pianistic tradition, he is particularly noted for lyrical, deeply felt interpretations of the great 19th century German and Austrian composers, especially Franz Schubert, Johannes Brahms, Ludwig van Beethoven, and Wolfgang Amadeus Mozart. He is also noted for performances of works by Czech composer Leos Janácek, and Hungarian composer Béla Bartók.
Lupu made his American debut in 1972 with the Cleveland Orchestra, with Daniel Barenboim conducting in New York City, and with the Chicago Symphony Orchestra, with Carlo Maria Giulini conducting. He made his San Francisco Symphony debut in 1974, when he performed Edvard Grieg's Piano Concerto, with Seiji Ozawa conducting. In 1984, he was featured in the "Peerless Pianists" series of the Lincoln Center Great Performers program in New York.
Although Lupu has performed with all of the major orchestras of the world and at major music festivals, he is a somewhat reclusive figure. He has regularly refused to grant interviews to journalists for over 30 years. In one rare published interview, originally from 1991, Lupu expressed his philosophy of music-making as follows:
""Everyone tells a story differently, and that story should be told compellingly and spontaneously. If it is not compelling and convincing, it is without value."
Ivry also reports that Mr. Lupu does not use a piano bench, but instead an office chair, when he concertizes.
Lupu has participated in notable chamber-music partnerships with, among others, the violinist Szymon Goldberg, the soprano Barbara Hendricks, and his fellow pianist, Murray Perahia.