Brendel was born in Wiesenburg (now Loučná nad Desnou), Czechoslovakia (now Czech Republic) into a non-musical family. They moved to Zagreb when Brendel was six, and later to Graz. They lived there during World War II, towards the end of which the fourteen year old Brendel was sent to Yugoslavia to dig trenches. However, he caught frostbite and was taken to hospital. Throughout his childhood, Brendel had occasional piano lessons, but otherwise little formal music education.
After the war, Brendel composed music, as well as continuing to play the piano and paint. He never had any more formal piano lessons, however, and although he did attend masterclasses with Edwin Fischer and Eduard Steuermann, he is largely self-taught.
Brendel gave his first public recital in Graz at the age of seventeen. He called it "The Fugue In Piano Literature", and as well as fugal works by Johann Sebastian Bach, Johannes Brahms and Franz Liszt, it included some of Brendel's own compositions. However, he gave up composing shortly after this to concentrate on the piano. In 1949 he won the Ferruccio Busoni Piano Competition in Bolzano, Italy and moved to Vienna the following year. At the age of 21, he made his first record, Sergei Prokofiev's Piano Concerto No. 5. He went on to make a string of other records, including a complete set of the Beethoven piano sonatas.
Brendel recorded extensively for the Vox record label, but did not get a major recording contract until the 1970s, nor did he play much outside Austria. His breakthrough came after a recital of Beethoven at the Queen Elizabeth Hall in London, the day after which three major record labels called his agent. Around the same time he moved to London. Since then, he has recorded extensively, and his fame has grown.
Brendel is today seen as one of the most thoughtful interpraters of classical Germanic works by composers such as Beethoven, Franz Schubert and Wolfgang Amadeus Mozart. He plays relatively few 20th century works, but is closely associated with the piano concerto of Arnold Schoenberg. In recent years, however, he has stopped playing many of the most physically demanding pieces in the repertoire, such as the Hammerklavier Sonata of Beethoven, owing to problems with arthritis.
Brendel's playing is sometimes described as being analytic, and he has said that he believes the primary job of the pianist is to respect the composer's wishes without showing off himself, or adding his own spin on the music. "I am responsible to the composer, and particularly to the piece," he has said. As well as his old teacher, Edwin Fischer, he cites Alfred Cortot, Wilhelm Kempff, and the conductorss Bruno Walter and Wilhelm Furtwängler as particular influences.
In recent years, Brendel has worked with young pianists such as Paul Lewis and Till Felner. He has also published poetry, which has been compared by Andrew Motion to Miroslav Holub in its style. He still lives in London.