Born into a clerical Parsi family, Jamsetjee Jeejeebhoy flouted the religious taboo on tobacco and alcohol to amass a fortune from the Opium trade with China. He diversified his interests soon after, and was a shareholder in Bombay's first English newspaper, "Bombay Courier". During the cotton boom he held 13 directorships in various cotton mills.
By 1829 he had become one of the leading members of his community. This is evident from the fact that as one of the four Akabars of the Parsi Panchayat he was made a trustee for the administration of funds for this body.
He became active in Parsi political life, and was a visible patron of educational and social reforms in the mid-nineteenth century. He donated a total of 234,272 pounds to the city, of which 113,380 went towards charities meant for his community. He was knighted in 1843.
In 1848 when a moribund Parsi Panchayat was trying to get the British government to recognise it as the representative organisation of the Parsis, he challenged it to prove its legitimacy by working for the community's poor instead. A year later he followed up this broadside, published as the book Kholas-i-Panchayat, by establishing the "Sir Jamsetjee Jeejeebhoy Parsi Benevolent Fund". This charity was eventually combined with the Panchayat's trust.
In 1849 he founded the city's first Parsi school and 14 years later also started the first school for Parsi priests, "Sir Jamsetjee Jeejeebhoy Zarthoshti Madresa". His patronage was sought by the more politically inclined of Bombay's citizens, as is clear from the fact that in 1852 he was elected to the managing committee of the "Bombay Association".
When the government refused to build a causeway to connect the island of Salsette to Bombay, Sir Jamsetjee Jeejeebhoy's wife, Avabai paid for it entirely on her own. Work on the Mahim Causeway started in 1841 and was completed 4 years later.