The crowd at Indore's Holkar Cricket Stadium witnessed two milestones as Sehwag's breath-taking 149-ball knock, studded with seven sixes and 25 fours, powered India to a massive 418 for five wickets, their highest ever ODI total.
In reply, West Indies simply caved in under the run mountain and barring Denesh Ramdin (96), none of their batsmen could provide substantial resistance as the visitors folded for 265 with four balls to go.
Ravindra Jadeja (3-34) was the pick of the Indian bowlers but debutant leg-spinner Rahul Sharma (3-43) impressed too.
Chennai hosts the fifth and final one-dayer on Sunday.
The day belonged to Sehwag, who toyed with the West Indies attack and scored almost at will.
Leading the side in absence of regular skipper Mahendra Singh Dhoni, Sehwag won the toss and returned to vindicate his decision to bat first on a belter of a track.
Sehwag added 176 runs with Gautam Gambhir (67) in 22-odd overs before a mix-up resulted in the exit of his opening partner.
Next man in Suresh Raina (55) also helped himself to an easy half-century before departing in a similar fashion.
None of these really affected Sehwag's natural game as sixes and fours continued to flow from his blade.
The visitors made it worse with their sloppy fielding.
Sehwag was on 20 when Kieron Pollard's direct hit missed the stumps with the batsman nowhere near the crease.
The double century would not have materialized either had Darren Sammy, running from extra cover, taken an easy catch off Ravi Rampaul. Sehwag was batting on 170 at that stage.
Sehwag grabbed the opportunity with both hands and cut Andre Russell for a boundary to overtake Sachin Tendulkar's 200 not out that was scored against South Africa in a Gwalior ODI on Feb 24, 2010.
Pollard eventually removed a tired Sehwag in the 47th over but the batsman by then had ensured India posted their fourth 400-plus total in one-day cricket.
