Upon graduating, Palkhivala applied for a position as lecturer at Bombay University, but was not awarded the post. Soon found himself trying to obtain admission to institutions of higher learning to further his academic career. It being late in the term, most courses were closed, and he enrolled at Government Law College, Bombay, where he discovered that he had a gift for unravelling the intricacies of jurisprudence.
Nani Palkhivala was called to the bar in 1944 and served in the chambers of the legendary Sir Jamshedji Behramji Kanga in Bombay. He quickly gained a reputation as an eloquent and articulate barrister, and was often the center of attention in court, where students of law and younger members of the bar association would flock to watch him.
His excellent court craft and an extraordinary ability to recall barely-known facts rendered him an irresistible force.
Not only did Nani Palkhivala interpret the constitution as a message of intent, he also saw it as a social mandate with a moral dimension. As he later stated in the Privy Purse case [Madhav Rao Jivaji Rao Scindia vs Union of India, (1971) 1 SCC 85]: "The survival of our democracy and the unity and integrity of the nation depend upon the realisation that constitutional morality is no less essential than constitutional legality. Dharma (righteousness; sense of public duty or virtue) lives in the hearts of public men; when it dies there, no Constitution, no law, no amendment, can save it."
He was a strong proponent of the rights of freedom of expression and freedom of the press. In an attempt to stifle dissenting opinion, the central government imposed import controls on newsprint in 1972. In the case before the Supreme Court [Bennett Coleman & Co. vs Union of India, (1972) 2 SCC 788], Palkhivala argued that newsprint was more than just a general commodity : "Newsprint does not stand on the same footing as steel. Steel will yield products of steel. Newsprint will manifest whatever is thought of by man."
Nani Palkhivala received honorary doctorates from Princeton University, Rutgers University, Lawrence University, University of Wisconsin–Madison, Annamalai University, Ambedkar Law University and the University of Mumbai.
In the last years of his life, Nani Palkhivala was severely affected by Alzheimer's disease. According to Attorney-General Soli J. Sorabjee, who had known him for many years, "it was painful to see that a person so eloquent and articulate unable to speak or recognize persons except occasionally in a momentary flash.
"Nani was taken critically ill on December 7, 2002, and taken to Jaslok Hospital in Mumbai. He died on Wednesday, December 11, 2002. He was 82.