[1] He was a Union Cabinet Minister of Health and Family Welfare and Shipping in the Atal Bihari Vajpayee government.

Sinha got his first acting opportunity to play a Pakistani military officer in Dev Anand's Prem Pujari.

He played supporting roles in Khilona, Dulal Guha's Dost in 1974, Aa Gale Lag Jaa, Jheel Ke Us Paar and Gambler in 1970.

Sinha played the lead hero were Ab Kya Hoga, Khan Dost, Yaaraon Ka Yaar, Dillagi, Vishwanath, Muqabla and Jaani Dushman.

He co-starred with Sanjeev Kumar in Bereham, Hathkadi, Baad Aur Badnaam, Chehre Pe Chehra, Hirasat and Qatl.

He has sung the song "Ek Baat Suni Hai Chachaji" with singer Sushma Shrestha in the film Naram Garam in 1981, composed by R. D. Burman.

However, when his films as lead hero like Prakash Mehra's Jawalamukhi, Amjad Khan's Chor Police, Ameer Aadmi Garib Aadmi and Raj Khosla's Mera Dost Meraa Dushman became flops, despite being appreciated by critics, there was threat to his career as lead hero.

His other hit films in the mid-eighties included Jeene Nahi Doonga, Bhawani Junction, Aandhi-Toofan, Ramkali, Ilzaam and Asli Naqli.

On 3 October 2009, Sinha appeared on Sony Entertainment Television Asia's show Dus Ka Dum season 2 as host for a special episode.

He portrayed Chief Minister Konda Shivaji Rao, a character based on NTR in Ram Gopal Varma's Rakta Charitra.

In March 2022, Sinha joined All India Trinamool Congress to contest in the By-election for the Asansol Lok Sabha constituency.

[18][19] On 16 April 2022, Sinha won by defeating Bharatiya Janata Party's Agnimitra Paul by a margin of 303,209 votes.

[20][21][22] In Lok Sabha Election 2024, Shatrughan Sinha won from Asansol seat, he defeated BJP's Surendrajit Singh Ahluwalia by a margin of 59564 votes.