Famously only five-foot (152 centimetres) tall, Mukherjee entered parliament in 1969 and looks set to end his long career in the turbulent world of Indian politics with a stint in the largely ceremonial role of president.
Known as a workaholic, a trouble-shooter and a shrewd tactician, he has been a leading figure within the ruling Congress party since the early 1980s when the country was governed according to socialist ideals.
He stood down as finance minister last month to run for president after serving in the post for three years during which India's increasingly market-driven economy has faltered, with growth falling sharply.
"The life of a finance minister is not easy," he told parliament when delivering his final budget in March. "When things go wrong, it is the finance minister who is called upon to administer the medicine.
"As Hamlet, the Prince of Denmark, said in Shakespeare's immortal words, 'I must be cruel only to be kind.'"
But the supposedly tough budget was quickly dismissed as ineffectual, and he leaves the finance ministry after the economy grew by just 5.3 percent between January and March -- its slowest quarterly expansion in nine years.
With the rupee also at record lows against the dollar, Mukherjee heads to the presidency with his reputation in poor shape compared to when he steered India through the 2009 global financial downturn.
Nevertheless he has retained the respect of a wide spectrum of Indian politicians and is seen as an ardent proponent of "inclusive growth" that would ensure that India's poor share in the country's development.
"The aim is to create an enabling atmosphere for corporates, farmers, entrepreneurs and workers to take initiatives for robust growth," he concluded in his March budget.
"The aim is also to ensure that the benefits of growth reach all sections of population."
Born on December 11, 1935 in the small village of Mirati in West Bengal, Mukherjee's father was a "freedom fighter" for India's independence movement who spent more than 10 years in British jails.
Mukherjee, who speaks with a heavy Bengali accent that his colleagues call "Pranabese", began as a college teacher and later worked for the Bengali publication Desher Dak ("Call of the Motherland") before entering politics.
He followed in his father's footsteps in joining the Congress party and was elected to the upper house in 1969 before moving to the lower house in 2004.
Once tipped as a future prime minister, his moment never arrived and a new generation of Congress leaders is being touted to take over when Premier Manmohan Singh, 79, stands down, most likely at the 2014 general elections.
Asked if he would serve in a Congress cabinet in the next parliament, Mukherjee has said: "There is a limit beyond which you cannot go. How long do you expect me to stay? Rather, I have overstayed my wicket."
But Mukherjee, who has been on the board of governors of the International Monetary Fund, the World Bank and Asian Development Bank, may take a more active approach to presidential duties than his predecessor.
Mukherjee, who sometimes stands on a box when giving speeches so he can see over the podium, lists his hobbies as gardening, reading and listening to music, and now he may also find more time for his wife, two sons and daughter.
His son Abhijit has followed in his father's footsteps, last year winning a seat in the West Bengal assembly as a Congress party candidate.
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