Munde, 64, is survived by his wife Pradnya and three daughters, including Maharashtra legislator Pankaja Munde-Palve. (Agencies)
The news of his death was confirmed by senior Cabinet Minister Nitin Gadkari to media persons at the AIIMS Hospital where Munde was rushed for treatment.
According to initial reports, Munde suffered serious internal injuries in the head and chest, but later succumbed to a massive heart attack during treatment.
This is the second mega-tragedy for one of Maharashtra top political families comprising the Munde-Mahajan clans.
Barely eight years ago, in April 2006, Munde's brother-in-law and senior BJP leader Pramod Mahajan was shot and grievously injured by his brother Pravin, at his Worli home.
Munde was married to Pramod's sister Pradnya. Mahajan, 56, succumbed to the injuries May 3 that year, plunging the BJP in a state of shock at the passing of its charismatic and youthful leader, who also served as a union minister handling different portfolios in the AB Vajpayee cabinet.
Following Mahajan's death, Munde was catapulted as the most important BJP leader in the state until the advent of the Gadkari who became the BJP president in 2010 - leading to a tussle for supremacy in state politics.
At the same time, the BJP chose Munde to be the party's deputy leader of opposition in the Lok Sabha, and Prime Minister Narendra Modi made him a cabinet minister, handling crucial portfolios.
The late Mahajan's daughter, Poonam Mahajan-Rao was swept to victory in the 2014 Lok Sabha elections from Mumbai North-Central constituency, defeating Congress's Priya Dutt, while her uncle Gopinath Munde was re-elected to parliament from Beed.
Similarly, Munde's daughter Pankaja Munde-Palve is active in state politics and is a state legislator from Parali, a constituency in her native Beed district in Marathwada region.
The other important leaders in the clan are Pandit Anna Munde (Gopinath's brother) and his son Dhananjay (Gopinath's nephew), both of whom quit the BJP to join the Nationalist Congress Party.
Munde's death is also the second big blow to the backward Marathwada region of the state in the past couple of years.
Barely two years ago Aug 14, 2012, the Congress' charismatic union minister and former state chief minister Vilasrao Deshmukh, 67, died following a prolonged illness.
Later that year, Maharashtra was plunged into grief when Shiv Sena supremo Bal Thackeray died Nov 17, 2012.
For the BJP, Munde's death will be deeply felt as he was one of the few grassroots leaders who toured the remotest parts of the state during his political career spanning over four decades.
Munde, 64, is survived by his wife Pradnya and three daughters, including Maharashtra legislator Pankaja Munde-Palve.