Ambani joined Reliance in 1981. At 24, he was put in charge of the company's Patalganga petrochemical plant. He took on a growing role as his father's health declined in the late 1980s, and led Reliance's expansion into petrochemicals, oil refining and gas.
He led the creation of the Jamnagar refinery in Gujarat, described as the world's largest grassroots petroleum refinery, with a capacity of about 660,000 barrels per day (2010).
After Dhirubhai Ambani's death in 2002, ownership of the Reliance group was divided between Mukesh and his brother Anil, with Mukesh retaining Reliance Industries.
Reliance launched Jio's 4G services in 2016, transforming India's telecom market with low-cost data. Jio later grew to over 500 million customers. At Reliance's 48th AGM in August 2025, Ambani announced plans to list Jio and unveiled Reliance Intelligence, a new artificial-intelligence subsidiary, along with partnerships with Google and Meta. In October 2026, Jio Platforms opened its IPO (21–23 October), reported as India's biggest-ever public offering.
In FY2025, Reliance reported consolidated revenue of ₹10,71,174 crore (about US$125 billion), the first Indian company to cross that mark.