Begum Akhtar's good looks and sensitive voice made her an ideal candidate for a film career in her early years. When she heard great Musicians like Gauhar Jaan and Malak Jan, however, she decided to forsake the glamour of the film world for a career in Indian classical music. Her supreme artistry in light classical music had its moorings in the tradition of pure classicism. She chose her repertoire in primarily classical modes: a variety of raags, ranging from simple to complex. After the advent of talkie era in India, Begum Akhtar acted in a few Hindi movies in the 1930s. East India Film Company of Calcutta approached her to act in "King for a Day" (alias Ek Din Ka Badshah) and Nal Damayanti in 1933.

Her first public performance was at the age of fifteen. The famous poet Sarojini Naidu appreciated her singing during a concert which was organised in the aid of victims of the 1934 Nepal–Bihar earthquake. This encouraged her to continue singing ghazals with more enthusiasm. She cut her first disc for the Megaphone Record Company, at that time. A number of gramophone records were released carrying her ghazals, dadras, thumris, etc. She was amongst the early female Singers to give public concert, and break away from singing in mehfils or private gatherings, and in time came to be known as Mallika-e-Ghazal (Queen of Ghazal).

Like others of that era, she sang her songs herself in all her films. She continued acting in the following years. Subsequently, Begum Akhtar moved back to Lucknow where she was approached by the famous producer-director Mehboob Khan, to act in Roti which was released in 1942 and whose music was composed by the Maestro Anil Biswas. "Roti" contained six of her ghazals but unfortunately due to some trouble with the Producer, Mehboob Khan subsequently deleted three or four ghazals from the film. All the ghazals are available on Megaphone gramophone records. Begum Akhtar, meanwhile, left Bombay and returned to Lucknow.

In 1945, Akhtari Bai married a Lucknow-based barrister, Ishtiaq Ahmed Abbasi, and became known as Begum Akhtar. However, after marriage, due to her husband's restrictions, she could not sing for almost five years and subsequently, fell ill. That is when her return to music was prescribed as a befitting remedy, and in 1949 she returned to the recording studios. She sang three ghazals and a dadra at Lucknow All India Radio station. She wept afterwards and returned to singing in concerts, which she continued to do unto death. She sang publicly in Lucknow, in a women's only concert in aid of the war, which was held in 1962.

She died on 30 October 1974 in the arms of Nilam Gamadia, her friend, who invited her to Ahmedabad, which became her final performance.

Her disciples include Shanti Hiranand, who later received Padma Shri and wrote, a biography Begum Akhtar: The Story of My Ammi (2005). Art critic S. Kalidas directed a documentary on her titled Hai Akhtari.

On October 7, 2017, Google dedicated a Doodle commemorating the 103rd birthday of Begum Akthar.

Her tomb was a mango orchard within her home, ‘Pasanda Bagh’ in Thakurganj area, of Lucknow. She was buried alongside her mother, Mushtari Sahiba. However, over the years, much of the garden has been lost to the growing city, and the tomb has fallen into disrepair. The marble graves enclosed in a red brick enclosure, were restored in 2012, along with their pietra dura style marble inlay. Attempts are on to convert her home built in 1936 in China bazaar, Lucknow into a museum.