The stylish left-hander, playing his first one-dayer in 16 months, hammered three sixes and 11 fours to help India reach their highest total against the West Indies on Sunday.
Ganguly received valuable support from another man making a comeback -- Gautam Gambhir, who scored a solid 69 in his first match after nine months. The left-handed pair put on 144 for the opening wicket.
Mahendra Dhoni (62 not out) and skipper Rahul Dravid (54 not out) then built on the openers' efforts, exploding with a flurry of boundaries to add 119 for the unfinished fourth wicket in the closing 11.5 overs.
The partnership helped the hosts surpass their previous best total of 325-5 against the West Indies.
West Indies skipper Brian Lara's decision to put India in to bat after winning the toss failed to produce the desired result as his team had to wait for nearly 25 overs for the first success.
Off-spinner Chris Gayle provided the breakthrough when he had Gambhir caught cutting by Marlon Samuels at backward point. Gambhir hit 10 fours in his second half-century in one-dayers.
But there was no stopping Ganguly, who batted comfortably against both seamers and spinners. His aggressive batting helped India maintain an impressive run-rate from the beginning.
Ganguly put on 70 for the second wicket with Sachin Tendulkar, a regular opener batting at the number-three position in this match. Tendulkar contributed 31 before being trapped leg-before by Gayle.
Ganguly looked set to complete his 23rd century when he was run out following a superb piece of fielding by Dwayne Smith, who picked the ball cleanly and hit the stumps at the non-striker's end.
Runs came thick and fast after Ganguly's dismissal as Dhoni and Dravid dominated the attack in the later stages to help their team set a stiff target.