Khakhar worked as an accountant for many years partnering with Bharat Parikh & Associates in Baroda Gujarat India., pursuing his artistic inclinations in his free time.

[citation needed] In 1958, Khakhar met Gujarati poet and painter Ghulam Mohammed Sheikh, who encouraged Khakar to visit the newly founded Faculty of Fine Arts in Baroda.

His first exhibited works presented deities cut from popular prints, glued onto mirrors, supplemented by graffiti and gestural marks.

The painter took special care to reproduce the environments of small Indian shops in these paintings, and revealed a talent for seeing the intriguing within the mundane.

The artist explored his own homosexuality in extremely personal ways, touching upon both its cultural implications and its amorous and erotic manifestations.

[9] In You Can't Please All[10] (1981; London, Knoedler's) a life-size naked figure, a self-portrait, watches from a balcony, as father, son and donkey enact an ancient fable, winding through the townscape in continuous narration.

[11][12] Among other honours, he won the Asian Council's Starr Foundation Fellowship, 1986, and the prestigious Padma Shri (Indian Government's award for excellence) in 1984.