Kumar made his film debut with a small role in Hum Hindustani in 1960. His first film as a protagonist was in Nishan (1965). In 1968, he acted alongside the famous actor of that time, Dilip Kumar, in Sangharsh.

He starred in the 1966 Gujarati film Kalapi, which was based on the poet Kalapi's life, with Kumar playing the titular role, Padmarani playing the role of his wife, Rama, and Aruna Irani as the love interest. The film was directed by Manhar Raskapur. Later Aruna Irani was paired opposite Sanjeev in another Gujarati film, Mare Javun Pele Par (1968).

He did three films opposite famous Tamil Actress L. Vijaya Lakshmi, including Husn Aur Ishq and Badal which became hits. Their first film was Alibaba Aur 40 Chor which was unsuccessful. His Raja Aur Runk, released in 1968, was a great success. He did Kangan, Rivaaz, Zindagi, Beraham, Archana and Do Ladkiyan opposite Mala Sinha. He did Priya, Anubhav, Gustaaki Maaf, Bachpan and Khud-Daar with Tanuja. He was paired with Rakhee in Angaare, Paras, Trishna, Shriman Shrimati and Hamare Tumhare. His hits with Leena Chandavarkar included Apne Rang Hazar, Manchali and Anhonee. He was paired regularly with Sulakshana Pandit in films such as Uljhan and Waqt Ki Deewar and with Moushmi Chatterjee in Itni Si Baat and Daasi.

In 1970, the movie Khilona, which was remake of Tamil film Engerindho Vandhaal, brought Kumar national recognition. In 1972, he played in an Indo-Iranian film, Subah aur Shaam. This was when Director Gulzar first spotted him. Later he cast Kumar in the roles of older men in 4 films Parichay, Koshish (1973), Aandhi (1975) and Mausam (1975). Gulzar casted Kumar in role of young man in the films Angoor (1981) and Namkeen (1982). Kumar won the BFJA Awards for Best Actor (Hindi) for his exemplary portrayal of a deaf and mute person in Koshish, in which the female lead was played by Jaya Bhaduri, who acted as his deaf and mute wife and was herself nominated for Best Actor award by Filmfare for the same role. He went on to star in the box office hits Seeta Aur Geeta (1972), Manchali (1973) and Aap Ki Kasam (1974). In 1973, he made a guest appearance during a song in a Tamil movie, Bharatha Vilas (1973). He performed in nine movies directed by Gulzar. Hrishikesh Mukherjee directed him in Arjun Pandit, for which he won the Filmfare Best Actor Award.

Kumar remained single all his life. He had proposed to Hema Malini in 1973 and they remained in touch even after he suffered his first heart attack in 1976. Later he was involved with Actress Sulakshana Pandit, but both of them remained unmarried. Kumar refused to marry her, as a result of which Sulakshana vowed to never marry anyone.

The producers and Directors of the South wanted to remake their Tamil and Telugu films in Hindi with either Kumar or Rajesh Khanna in lead. It was these Hindi film remakes which elevated him to a great actor. The film Khilona and its Tamil version Engirundho Vandhaal were made simultaneously. Navarathri was remade as Naya Din Naya Raat. Kumar reprised the role played by Thengai Srinivasan in Yehi Hai Zindagi which was a remake of Kaliyuga Kannan. He starred as lead in the film Shaandaar in 1974 which was a remake of Kasturi Nivasa which had Kannada actor Rajkumar in the lead. He enacted the role played by AVM Rajan in Anadhai Aanandhan, in its Hindi version Chand Aur Bijli in 1970. Gnana Oli was remade as Devata in 1976 with Kumar reprising the role originally paid by Sivaji Ganesan. He also acted in the Telugu remake of Swargam Narakam, as Swarg Narak (1978). Though the film Suraag was a hit, during the mid 1980s, Northern Indian producers and Directors casted Sanjeev Kumar primarily in supporting roles in films like Khudaar, Sawaal, Zabardast, Hero and Silsila. However southern Indian Directors casted him in lead roles even in the period 1980 to 1985. He played the role which N.T. Rama Rao did originally in Devina Chesina Manushulu, in its Hindi version Takkar in 1980. Tayaramma Bangarayya was remade as Shriman Shrimati in 1982, Raman Ethanai Ramanadi was remade as Raam Kitne Tere Naam in 1985. Kumar reprised the role played by R.Muthuraman in Alukuoru Aasai in its Hindi remake Itni Si Baat in 1981. Sivaji Ganesan gave Kumar a role in his own home production Gauri (1968), which was a remake of Shanti (1965). The role played by S.S. Rajendran in Shanti was re-enacted by Kumar in Gauri.

His performances in films such as Charitraheen, Angaare, Grihapravesh, Chehre Pe Chehra, Sawaal and Yaadgaar, though they became-box office flops, were appreciated by critics and during their subsequent screening on television. Kumar always demonstrated a willingness to take on unconventional roles that challenged him as an actor. His role as Mirza Sajjad Ali, a chess-obsessed Lucknowi (citizen of Lucknow), in Satyajit Ray's classic Shatranj Ke Khilari (1977) exemplified that aspect. Perhaps his best remembered roles were in the blockbuster films Sholay (1975) and Trishul (1978). His portrayal of the character Thakur, from Sholay, released in August 1975 was one of his stellar performances. In Naya Din Nayi Raat (1974), Sanjeev Kumar reprised the nine-role epic performance by Sivaji Ganesan in Navarathri (Tamil; 1964), which was also previously reprised by Akkineni Nageswara Rao in Navarathri (Telugu; 1966). This film enhanced his status and reputation as a serious player in Bollywood. He stood his ground against leading superstars such as Rajesh Khanna in Bandhan and Aap Ki Kasam; Amitabh Bachchan and Shashi Kapoor in the Yash Chopra multi-star cast film Trishul (1978) and Dilip Kumar in the film 'Sangharsh' and Vidhaata (1982).

He has done many regional films in different languages including Marathi, Punjabi, Tamil, Telugu, Sindhi and his mother tongue Gujarati.In 1980, he starred in the Punjabi movie Fauji Chacha.He made guest appearances in two Tamil filmsm Bharata Vilas and Uyirandhavargal (a remake of Koshish).

Sanjeev Kumar's excellent comic timing entertained audiences in films such as Seeta Aur Geeta, Biwi O Biwi (1981), Pati, Patni Aur Woh, Angoor (1982) and Hero (1983).

Kumar was born with a congenital heart condition, and many members of his family had not lived past 50. After his first heart attack, he underwent a bypass in the US. However, on 6 November 1985, at the age of 47, he suffered a massive heart attack, which resulted in his death. His younger brother Nikul died before him, while his other brother Kishore died six months later. Ironically for an actor who had played many elderly roles, he died at less than 50 years of age.

Over ten movies starring Sanjeev Kumar were released after his death, with the last one, Professor Ki Padosan, released in 1993. At the time of his death, only about three-fourths of this movie was complete, and it was eventually decided to alter the story line in the second half to explain the absence of Kumar's character.

A postage stamp bearing his likeness was released by India Post to honour him on 3 May 2013.

An auditorium was opened in his home town Surat by the Gujarat State at the cost of 108cr, named Sanjeev Kumar Auditorium, which was inaugurated on 14 February 2014 by Prime Minister Narendra Modi who was then the CM of Gujarat. He is the first and only (as of 2014) Indian film actor to have an auditorium named after him.

The Sanjeev Kumar Foundation is a national level development organisation (NGO) directly benefiting children and their families every year, mainly focusing on education, Health care, environment, culture and nutrition. From 2015 onwards the foundation has also been the sponsor of the annual Sanjeev Kumar Drama Competition held by the Surat Municipal Corporation. The awards and cash prizes are given in memory of Sanjeev Kumar to the best actor, Actress, Director and backstage technician every year.