Replying to the hosts' formidable score of 299/9, the England under-19 side were bundled out for 253 in 46.4 overs at the Maharaja Bir Bikram Stadium.
M Tehlan (51, 64b, 3x4) top scored for the Indians who opted to bat after their new captain Manoj Tiwari won the toss in the morning.
The English colts had a poor start losing two quick wickets before middle order batsmen M Ali (57, 72 balls, 7x4, 2x6), T Smith (56) and W Gifford (33, 55 b, 4x4) tried to rescue their side, but in the end the visitors fell well short of the Indian total.
India's Gaurav Dhiman, who scored 43 and claimed two wickets, was declared man of the match.
The second One-dayer will be played in the same ground on Wednesday.
Brief score: India 299/9 in 50 overs (M Tehlan 51, M Tiwari 46, Griffiths 2/48, Lawson 2/46).
England 253 all out in 46.4 overs (M Ali 57, T Smith 56; Dhiman 2/58, Sharma 2/20, Pradip 2/45).