Karunanidhi was admitted to the hospital on July 28 following a dip in his blood pressure. Since then he was monitored by a team of specialists.
Prime Minister Narendra Modi condoled the death of former Tamil Nadu chief minister, saying he was "deeply saddened by the passing away of Kalaignar Karunanidhi".
"Deeply saddened by the passing away of Kalaignar Karunanidhi. He was one of the senior most leaders of India. We have lost a deep-rooted mass leader, prolific thinker, accomplished writer and a stalwart whose life was devoted to the welfare of the poor and the marginalised," Modi tweeted.
President Ram Nath Kovind said: "Extremely sad to learn of the passing of Thiru M. Karunanidhi. A doyen of our public life, as a contributor to the development of Tamil Nadu and of India he has few peers. Our country is poorer today. My condolences to his family and millions of well-wisher."
ALSO READ: Who was DMK chief M Karunanidhi?
Thousands of DMK cadres have gathered outside the hospital in downtown Alwarpet to mourn the demise of the charismatic Dravidian leader.
Karunanidhi, one of the most senior politicians in India, was Tamil Nadu's Chief Minister five times but was ailing for some time.
Karunanidhi was out of active politics for the past two years owing to health reasons. He did not participate in any public function and only visited the party headquarters a few times during this period. He was elected from Tiruvarur in the 2016 Assembly polls.
Born on June 3, 1924, at Thirukuvalai, now in Nagapattinam district, Karunanidhi never lost an election, having been elected to the state Assembly 13 times since 1957.
Karunanidhi's remarkable literary skills and success as a screenwriter and subsequent popularity played a big role in his rise in the DMK and his overall stature.
Notably, movies like "Parasakthi" (1952) and "Manthirikumari" (1950), that had his sharp dialogues tinged with distinctive political overtones were super hits.
Amidst his success in the film world came his successful electoral debut in 1957 when he won from Kulithalai constituency, one among the first 15 MLAs elected to the then Madras Legislative Assembly on a DMK ticket.
The rest is history. He went on to become chief minister of the state for five times after the death of Annadurai in 1969 besides serving DMK as the party president.
Even during his last tenure (2006-11) he had written script for two films "Uliyin Osai" and "Pen Singam" and continues to write almost everyday in party mouthpiece "Murasoli" to cadres.
Karunanidhi was hooked to the Dravidian movement led by reformist leader Periyar EVR when he was still a teen.
He became an ardent follower of Dravidian ideologue CN Annadurai and joined the DMK when the latter founded it in 1949.
Endowed with brilliant screen-writing skills, he used it to further the ideology of DMK on-screen, primarily rationalism like his mentor Annadurai.
As its proponent, he too began rising as a star in films and politics and came to be hailed as "Kalaignar" (artist) in subsequent years by his supporters.
His sharp screen play in "Parasakthi," (1952) a trendsetter Tamil movie, would illustrate how films were used by DMK to propagate its ideals and ensconce itself deep in public consciousness which eventually aided it in capturing power from Congress in 1967.
Karunanidhi was Tamil Nadu Chief Minister five times between 1969-71, 71-76, 89-91, 96-01 and 2006-11.
Despite many ups and downs, he has not lost a single election himself. He debuted in Kulithalai in 1957 and went on to win in all the subsequent eleven elections he contested.
He did not contest the 1984 assembly election since he was a member of the Legislative Council then.