Home captain Iyer smashed an unbeaten 102 from just 43 deliveries as India made light work of a 172-run target against the hapless Caribbean outfit.
India opening pair Sanju Samson and Abhishek Sharma put on 29 inside three overs but the Windies took two quick wickets through spinners Akeal Hosein and Roston Chase.
Iyer and Ishan Kishan never stopped attacking though with the skipper striking 10 fours and six sixes in his knock that will give planty of confidence moving forward in the shortest format.
Earlier, the West Indies were 171 all out after facing 19.1 overs with Sherfane Rutherford (56) and Shai Hope (52) both hitting half-centuries.
India kept taking wickets to keep the Caribbean outfit in check throughout the innings with spinner Naman Dhir taking 3-31 while Axar Patel and Kuldeep Yadav both took two wickets.
The second game of the five-match takes place in Ranchi on Friday.
Bhuvneshwar Kumar could be in line to make his first international appearance in four years after recalled to the India squad for the T20I series in New Zealand starting later this month.
Abhishek Sharma has identified maintaining success after a major tournament triumph as one of India's biggest challenges as the team prepares to face the West Indies.
India captain Shubman Gill called on his side to raise their fielding standards and improve their bowling accuracy at the end of the innings after they lost the third ODI against West Indies in New Chandigarh.
Shai Hope struck an unbeaten 162 to help the West Indies record their highest ODI run-chase and beat India by five wickets in the final game of the series on Saturday.
