Though age was not on his side, the 87-year-old scriptwriter-politician shouldered the responsibility of steering the DMK back to power for the second consecutive term but failed in his attempt.
From interviewing hopeful contestants to selecting candidates among them to drafting the party's manifesto, Karunanidhi did it all.
Pitted against a formidable alliance stitched by his arch rival J Jayalalithaa, Karunanidhi convinced his partymen to contest in less number of seats and walked the extra mile with ally Congress but none of the strategy paid fruits.
For Karunanidhi, it was a tight rope walk ever since he began the alliance talks early January with party leaders cautioning him not to succumb to the pressure from Congress and other allies like PMK.
But, ignoring their advice, the wheel-chair bound DMK chief travelled all the way to Delhi and finalised the alliance with Congress President Sonia Gandhi.
And, more so, it was the DMK which blinked in the attrition battle with the Congress after the seat-sharing talks between the two allies broke down following which the regional party decided to pull out of the UPA government.
The party's defeat in the crucial polls could not have come at a worse time for Karunanidhi as the DMK finds itself in a vulnerable position more than ever, thanks to his daughter and party MP Kanimozhi being arraigned as a co-conspirator in the 2G spectrum scam.
Despite his old age, Karunanidhi addressed public meetings and undertook a whirlwind tour of the state and shared platforms with allies like Sonia Gandhi, PMK's S Ramadoss and VCK's Thol Thirumavalavan.
Joining the then fledgling anti-Hindi agitation at the young age of 14, Karunanidhi, who was born on June 3, 1924, moved to the Tamil film industry in 1950s and started penning dialogues and screenplays for movies.
Powerful dialogues in his debut movie 'Parasakthi', which starred his friend late thespian Shivaji Ganesan, made Karunanidhi a hit among the masses and there was no looking back after that.
Born into a middle class Nadaswaram vidwan family, Karunanidhi rose to dazzling heights from a student leader to one of the founding members of the DMK and Chief Minister for five terms through his political skills and manoeuvres.
Known for his wit and oratorical skills, qualities which helped his rapid rise as a popular politician in Tamil Nadu for past five decades, he was famous for writing historical and reformist stories which propagated the socialist and rationalist ideals of the Dravidian movement of which he was a product.
Inspired by the speech of Alagiriswamy, he joined the Justice Party, when he was 14 and organised the youth in his area as volunteers, in 1938, bringing out the inborn organisational skills in him.
When DMK founder late C N Annadurai broke away with his mentor E V Ramaswamy, Karunanidhi also came out with him and became one of the founding members of the party.
He campaigned among the DMK cadre in 1956 for the need to contest the polls and succeeded when an overwhelming majority of workers voted in favour of contesting the polls at a General Council meeting at Tiruchirapalli.
Karunanidhi entered the state assembly in 1957 from Kulithali in Karur district where he led an agitation against "Nandivaram Zamin" in support of farm workers there.
He never looked back from then and became the deputy leader of the opposition in 1962 and Public Works Minister in the first DMK ministry headed by Annadurai in 1967.
Though number three in the party then, he manoeuvred his way and got the support of the DMK MLAs to become the Chief Minister in 1969 after Annadurai died of cancer.
He relegated the then number two in the party late V R Neduchezhiyan not only to become the Chief Minister but also as the DMK President, the post he holds till today.
In 1972, he expelled the powerful treasurer of the party, Tamil film icon M G Ramachandran, when he levelled corruption charges against Karunanidhi and his cabinet colleagues, perhaps the only grave mistake he would have committed in his public life.
MGR, who became the Chief Minister in 1977, never allowed DMK to come to power till his death in 1987.
In the 1989 Assembly elections, Karunanidhi appealed to voters to give their mandate for him as he had already spent 14 years of vanvas like Lord Ram and it clicked.
But he was able to be in power only for over 18 months, when the then Prime Minister S Chandrashekar dismissed his government on the charge that it allowed a free run to the Sri Lankan Tamil militant group LTTE.
In the 1991 Assembly polls, DMK was marginalised as Karunanidhi and another DMK man Paruthi Ilamvazhuthi alone could win the polls. Karunanidhi resigned from the assembly then.
His party emerged victorious in the 1996 Assembly polls and was trounced in 2001, but came back to power in 2006.