Asha Bhosle suggested Padmini's name to Dev Anand, who then cast her in Ishq Ishq Ishq (1975). This led to other films, such as Dreamgirl (1978), Zindagi (1976), and Saajan Bina Suhagan (1978). She also gave a very commendable performance of a school girl inflicted by black magic in Gehrayee (1980).

Her mother quit her airlines job to be a full-time chaperone as Padmini picked up more roles. Her most famous child role was playing a child in Raj Kapoor's 1977 film Satyam Shivam Sundaram. Her success led to her most controversial role in Insaaf Ka Tarazu (1980), a remake of Lipstick (1976), where she played the rape victim that was originally played by Mariel Hemingway. She earned the Filmfare Best Supporting Actress Award for her performance. She graduated to heroine roles at the age of 15 in Nasir Hussain's Zamane Ko Dikhana Hai opposite Rishi Kapoor. The film flopped, but she reunited with Rishi for his father Raj Kapoor's film Prem Rog in 1982. The film earned her a Filmfare Best Actress Award. She earned a special acting award for Ahista Ahista.

Kolhapure, at the age of fifteen, won the Filmfare Award for Best Supporting Actress for her performance in the revenge drama Insaf Ka Tarazu (1981), and at the age of seventeen, won the Filmfare Award for Best Actress for the tragic romance Prem Rog (1983), thus becoming the second-youngest Actress to win the awards in the respective categories.

Padmini was known for her professionalism and diligence. She even worked when she had fever on Do Dilon Ki Dastaan. She had more box office hits, such as Vidhaata (1982) and Souten (1983). She had a huge hit with Pyar Jhukta Nahin (1985) with Mithun Chakraborty, and they were paired together in several more films. She agreed to work with Anil Kapoor when he was a newcomer in his first film Woh Saat Din (1983). The movie was a hit and helped cement his name in the Indian film industry; Anil Kapoor attributes his eventual success in the film industry to her "luck".

As a child, she sang in the chorus for songs in films such as Yaadon Ki Baaraat, Kitab and Dushman Dost with her sister Shivangi. Padmini later sang for her own films such as Vidhaata, Saat Saheliyan, Hum Intezaar Karenge and Sadak Chaap (with Kishore Kumar). She released an album with Bappi Lahiri titled Music Lovers. She performed for the Greater London Council at the Royal Albert Hall in London with Bappi Lahiri and his troupe in 1986.

After her son grew up, she returned to acting in 2004, such as for the Marathi films Manthan and Chimnee Pakhra, which was a huge hit and earned her a Screen Award in the Best Marathi Actress category. She appeared in the 2006 horror film Eight Shani. In 2011, she made her foray into Malayalam cinema with V. K. Prakash's Karmayogi, an adaptation of Shakespeare's Hamlet.

She appeared in Mera Bachpan with Helen in 2008. She has also acted on stage in Kaash, followed by Abhi To Mein Jawan Hoon and Aasman Se Gire Khajoor Pe Atke, with her brother-in-law Shakti Kapoor.