Saira spent a significant part of her childhood in London, and went to finishing school. Her maternal grandmother was from Hasanpur (Uttar Pradesh). Her paternal grandfather, Muhammad Suleman, was an Architect who served as the Chief Engineer of New Delhi and was later involved in the construction of Jinnah's Mazar in Karachi. Her paternal grandmother, Khatoon Begum, was from Old Delhi's Mohalla Churiwalan, and a daughter of the "raees" and public figure, Khan Bahadur Maulvi Abdul Ahad (1849-1920). Her paternal grand-aunt Khadeeja Begum, was married to the Shahi Imam of the Jama Masjid in Delhi, Ahmed Bukhari.

Saira Banu was 16 years old in 1960, the year she made her debut to Hindi films. She said in a programme that she had basic talent and little dancing experience. Her peers all were classically trained, which was why she wasn't put in the top league. Saira started taking Kathak and Bharata Natyam lessons with success, and trained herself professionally. Soon she became a Dancer, and her films flaunted more of her dance. Banu made her acting debut opposite Shammi Kapoor in the 1961 film Junglee, for which she earned her first Filmfare nomination as Best Actress. The famous song from this movie "Yaahoo!! Chahe Koi Mujhe Junglee Kahe" sung by Mohammed Rafi was a big success. Junglee was written by Aghajani Kashmeri (aka Kashmiri and Agha Jani), who also coached her in Urdu dialogue delivery, given his background in Urdu literature and poetry from Lucknow. Junglee also instantly made her a successful Actress throughout the 1960s and early 1970s. Her image was that of a romantic heroine for love stories in the 1960s, till 1967. She did one more film opposite Shammi Kapoor, named Bluff Master, directed by Manmohan Desai. Some of her successful romantic films include Jhuk Gaya Aasman and Aayi Milan Ki Bela, with Rajendra Kumar, and April Fool, with Biswajeet, and five films with actor Joy Mukherjee - Aao Pyaar Karen, Saaz Aur Awaaz, Door Ki Awaz, Yeh Zindagi Kitni Haseen Hai and Shagird. She did a double role in the film Yeh Zindagi Kitni Haseen Hai. After her marriage in 1966, her first film to release was Aman, opposite Rajendra Kumar, and she continued to act as the lead heroine till 1977. But it is said that the turning point of her career was the comedy and love story Padosan, in 1968, opposite Sunil Dutt, which brought her to the top league of the successful actresses, and she started receiving more offers.

Saira Banu married actor Dilip Kumar in 1966. Saira Banu was the third highest paid Actress in Hindi Cinema from 1963 to 1969 and the fourth highest paid Actress from 1971 to 1976.

Her films with Navin Nischol were very successful, such as Victoria No. 203 and Paise Ki Gudiya. In an interview, she quoted that she regretted missing the chance of working with Rajesh Khanna. She quoted: "I was supposed to work with him in Choti Bahu (1971), but I could not because I was ill. I shot with him for two days and found that he was very charming, humble and a shy person." She did earn three additional Filmfare nominations as Best Actress for Shagird (1967), Diwana (1968), and Sagina (1974).

She also did Pyar Mohabbat with Dev Anand and did three films with Manoj Kumar, namely Shaadi, Poorab Aur Paschim and Balidan. She established herself as a versatile Actress after her marriage, with her performances in Padosan, Victoria 203, Jhuk Gaya Aasman, Sagina and Chaitali - with each of them belonging to different genres. She was paired with Vinod Khanna in Aarop, wherein the song Naino mein darpan hai became a chartbuster in 1974. Her pairing with Sunil Dutt continued to be solid at the box office with films such as Nehle Pe Dehla being successful in 1976. The song "Sawan ka mahina aagaya" became very popular in 1976. However, with films such as Daaman Aur Aag, Mounto, Zameer and Koi Jeeta Koi Haara becoming disasters, and with some of her films being kept on hold for release, such as Faisla, Mera Vachan Geeta Ki Kasam and Aarambh, she decided to not sign for any more films. Hence in 1976, Saira chose to end her film career. Subsequently she weathered a storm in her marriage in 1980, when her husband married a girl named Asma, which was quickly resolved. She then appeared in a cameo opposite her husband in Duniya (1984), wherein the song "Teri meri zindagi" became very popular. Her last film; Faisla where she was cast opposite Vinod Mehra which was completed in 1976, released in 1988.

Her husband Dilip Kumar revealed in his 2014 memoir "Dilip Kumar: The Substance and the Shadow" that she became pregnant in 1972 with their son, but that she developed high blood pressure in her eighth month of pregnancy and the doctors couldn't save the baby, which had been strangulated by the umbilical cord. After that, they never had children, believing that it was God's will.