The tourists overcame a rollicking start by the hosts to bowl India out for 268 and then surpassed the challenging target in the 44th over under lights at the Chidambaram stadium.
Samuels and Lara put on a match-winning stand of 127 for the fourth wicket after opener Chris Gayle had fallen leg-before to Ajit Agarkar off the first ball of the innings.
Agarkar, who had Samuels caught behind two runs short of his third one-day century, finished with 3-45 and the West Indies lost three wickets for eight runs at the end before recording their first win in the four-match series.
Lara's men now travel to Vadodara for Wednesday's final match, hoping to draw their last series 2-2 before the Caribbean nations host the World Cup in March-April.
"That will be a big game for us, our last before the World Cup, and we will go out there fighting," said Lara.
"We have lost badly in the past but today we showed we can win well too. It was a commanding win, especially while bowling."
India's total revolved around a robust 70 off 42 balls from young opener Robin Uthappa and half-centuries from captain Rahul Dravid (57) and senior pro Sachin Tendulkar (60).
India, sent in to bat by Lara, were cruising at 232-3 in the 35th over when the tourists bounced back with seven wickets for 36 runs.
Seamer Dwayne Bravo, hammered for 19 runs by Uthappa in his first over, grabbed four wickets for 20 runs in his next eight to lead the West Indian revival.
Uthappa, a 21-year-old playing only his fourth one-dayer, enhanced his World Cup claims by smashing 11 boundaries and two sixes in his first appearance in the series.
When Uthappa fell in the 11th over, holing out in the deep off Gayle, he had contributed 70 runs in India's total of 95-2.
Tendulkar, one-day cricket's most successful batsman with 14,568 runs and 40 hundreds before this match, finally hit form after making just 202 runs in his last 10 innings.
Both Tendulkar and Dravid hit their 75th one-day half-centuries in a fourth-wicket stand of 106 before falling in the space of five runs to trigger the collapse.
"We should have got 330-340 on this very good wicket," said Dravid.
"We were just not good enough today although Uthappa showed how well he can take the opportunities that come his way.
"Vadodara will be an important game and I hope we can wrap up that one."
India's selectors, not hesitating to change and chop in a bid to arrive at the perfect World Cup combination, rested Sourav Ganguly, Harbhajan Singh, Mahendra Dhoni and Zaheer Khan for the match.
Yuvraj, fit again after suffering a knee ligament injury in November, returned to the team along with veteran spinner Anil Kumble.
Lara was back for the West Indies after missing the previous match in Cuttack on Wednesday with a sore knee.
The tourists rested in-form batsman Shivnarine Chanderpaul and brought in Lendl Simmons and Emrit for the first time in the series.