His father, François, a director of the French East India Company, sent Dupleix on a voyage to India and America in 1715. His father's influence led to his appointment (1720) to the superior council of Pondicherry (Puducherry) (now Puducherry), the capital of French India. He was made superintendent of the French factory (trading station) in Chandernagore, Bengal, in 1731 and 11 years later was appointed governor-general of all French establishments in India. When fighting between France and Britain broke out in the War of the Austrian Succession (Austrian Succession, War of the) in 1744, the French proposed neutrality in India, but this was rejected by the British. In 1746, with the help of a French fleet, Dupleix seized Madras (now Chennai) but failed to capture the neighbouring British fort of St. David. He twice defeated armies sent to relieve Britain's ally, the nawab Anwār al-Dīn of the Carnatic (modern Karnataka (Karnātaka) state).

The Treaty of Aix-la-Chapelle (Aix-la-Chapelle, Treaty of) ended the war in Europe in 1748 and restored Madras to the British, but Dupleix embarked on further schemes for French aggrandizement in India. Sensing the military weakness of the various contending princes in south India, he forged local alliances with them that were aimed at ruining the British East India Company. He supported Chanda Sahib's claim to the nawabship of the Carnatic, and, when the British supported a rival candidate, a largely private war ensued (1751) between the two companies. Mostly as the result of the exploits of Dupleix's chief rival, the brilliant young British soldier Robert Clive (Clive, Robert, 1st Baron Clive of Plassey), all the French forces except those in the Deccan were defeated. Dupleix's grand schemes continued to topple for two more years, and French finances were exhausted in the struggle.

In 1754 Dupleix was recalled to Paris, where he unsuccessfully sued the French East India Company for money he claimed he had spent on its account. Dupleix remained discredited in France and died in despair, obscurity, and relative poverty. He had displayed great talents as an organizer, diplomat, and imaginative political visionary, but he had lacked military acumen and the ability to work with others.