Born in 1934, Khakhar began his career in art fairly late in life, at the age of 38. Before that, he worked as a chartered accountant. In his late 30s, Khakhar decided that being a chartered accountant was not what he wanted to be doing for the rest of his life, so he joined the M.S. University at Baroda to study art criticism. He began painting with collages from calendar art. "I was interested in the expressionistic style, which had no wit and humor. Now I am more involved in wit, painting people, and the environment around me." A lot of his work done in the 70's is a depiction of trade, such as paintings of watchmakers, tailors and barbers.
Khakhar received international acclaim as an artist much before he got recognition in India. British artist Howard Hodgkin helped Khakhar organize a solo exhibition way back in the 1980s. In 1989,he held his solo exhibition at theWorld Trade Center in Amsterdam.
Among his inspirations, the painter counts David Hockney, the British master. Like Hockney's work, Khakhar's own initial paintings revolved around the everyday, 'insignificant man' trapped in an unremarkable existence. Khakhar also worked with his contemporaries in Baroda like Gulam Mohammed Sheikh, to evolve a visual language that combined traditional Indian art elements with contemporary themes. Then came what Khakhar calls his "gay period", in which, "I tried to explore and represent the world of homosexuals as I know and understand it." First came the small figures of male nudes. The figures got bigger and bigger, then came the solitary large male nudes and then two male nudes together.