Born on September 17, 1915 in Pandharpur in Maharashtra, Hussain was mainly a self-taught artist. He made ends meet in his initial days by painting cinema hoardings in Mumbai, paid barely four or six annas per square feet. As soon as he earned a little bit he used to take off for Surat, Baroda and Ahmedabad to paint landscapes. Hussain tried other jobs and one of the best paying was a toy factory where he designed and built toys.

Hussain first became well-known as an artist in the late 1940s. In 1947, he joined the Progressive Artists' Group, founded by Francis Newton Souza. This was a clique of young artists who wished to break with the nationalist traditions established by the Bengal school of art and to encourage an Indian avant-garde, engaged at an international level. In 1952, his first solo exhibition was held at Zurich and over the next few years, his works were widely seen in Europe and the US. In 1955, he was awarded the prestigious Padma Shri award by the Government of India.

In 1967, he made his first film, ‘Through the Eyes of a Painter’. It was shown at the Berlin Film Festival and won a Golden Bear. M F Hussain was a special invitee along with Pablo Picasso at the Sao Paulo Biennial in 1971. He was awarded the Padma Bhushan in 1973 and was nominated to the Rajya Sabha in 1986. He was awarded the Padma Vibhushan in 1991.

Hussain went on to become the highest paid painter in India. His single canvases have fetched up to $2 million at a recent Christie's auction.

He has also produced & directed few movies, including Gaja Gamini (with his muse Madhuri Dixit who was the subject of a series of his paintings which he signed Fida). The film was intended as a tribute to Ms. Dixit herself. In this film she can be seen portraying various forms and manifestations of womanhood including the muse of Kalidasa, the Mona Lisa, a rebel, and musical euphoria. He went on to make ‘Meenaxi: A Tale of Three Cities’ with Tabu. His autobiography is being made into a movie tentatively titled ‘The Making of the Painter’, starring Shreyas Talpade as the young Hussain. The Peabody Essex Museum (PEM) (USA, Massachusetts) showed a solo exhibition from 4 November 2006 to 3 June 2007. It exhibited Hussain’s paintings inspired by the Hindu epic, Mahabharata.

At the age of 92, Hussain was to be given the prestigious Raja Ravi Varma award by the Government of Kerala. The announcement led to controversy in Kerala and some cultural organizations campaigned against the granting of the award and petitioned the Kerala courts. Sabarimala spokesperson, Rahul Easwar, went to Kerala High Court and it granted an interim order to stay the granting of the award until the petition had been disposed of.

In early 2008, Hussain's ‘Battle of Ganga and Jamuna: Mahabharata’, a large diptych, from the Hindu epic, fetched $1.6 million, setting a world record at Christie's South Asian Modern and Contemporary Art sale.

His name was included in the list of the 500 Most Influential Muslims in the World, issued by the Royal Islamic Strategic Studies Center in Amman, Jordan.

For the last years of his life he lived in Dubai and London, staying away from India, but expressing a strong desire to return, despite fears of arrest.