Kher made his acting debut in the 1982 Hindi movie Aagman. Then in 1984 came Saaransh, where he played a retired man who has lost his son. He hosted TV shows such as Say Na Something To Anupam Uncle, Sawaal Dus Crore Ka and the recent Lead India. He has had many comic roles but has also played the villain such as his acclaimed role as terrorist Dr. Dang in Karma (1986). For his role in Daddy (1989) he received the Filmfare Critics Award for Best Performance. Kher has won the Filmfare Award for Best Performance in a Comic Role five times, more than any other actor.
He has starred alongside Bollywood superstar Shahrukh Khan many times in films such as Darr (1993), Dilwale Dulhaniya Le Jayenge (1995), Chaahat (1996), Kuch Kuch Hota Hai (1998), Mohabbatein (2000) and Veer-Zaara (2004).
He ventured into directing with Om Jai Jagadish (2003) and has also been a producer. He produced and starred in the film Maine Gandhi Ko Nahin Mara (2005). He received the Best Actor Award from the Karachi International Film Festival for his performance in the film.
Kher is known internationally for Bend It Like Beckham (2002), Bride and Prejudice (2004), his appearance on the hit TV show ER, and most recently in The Mistress of Spices (2006) and Lust, Caution (2007).
Kher has written and starred in a play about his own life called Kuch Bhi Ho Sakta Hai, which is directed by Feroz Abbas Khan.
Until recently he served as chairman of the Indian Film Censor Board. He is an alumnus of National School of Drama (1978 batch) and was its director between 2001 and 2004.
In 2007, Anupam Kher, with his batchmate of NSD, Satish Kaushik started a film production company, Karol Bagh Productions. Their first film, Tere Sang, is being directed by Satish Kaushik.
He has recently been appointed the goodwill ambassador of the Pratham Education Foundation, which strives to improve children’s education in India.
He also starred in a number of Punjabi films such as Yaaraan naal bahaaraan.
He is also widely regarded as an intellectual talk show participant