Rohit Sharma helped India put on a 45-run opening stand after Hong Kong opted to bowl, but soon perished to the first over of spin, bowled by Ehsan Khan.
Shikhar Dhawan went on to score a hundred, driving India after Rohit Sharma's wicket.
Ambati Rayudu made 60 runs, returning to the Indian side after missing the England tour owing to fitness issues.
India lost 3 wickets for 8 runs in the middle order, which included MS Dhoni's wicket on nought. Kedar Jadhav hit one six in his 27-ball 28 to take India to 285 in the designated 50 overs.
Anshuman Rath and Nizakat Khan played India's pace bowlers with aplomb, bringing up Hong Kong's highest ever opening stand in ODIs
Nizakat Khan starred with a half-century brought off 47 balls.
Kuldeep Yadav had Anshuman Rath caught at cover to end the opening stand, and it was downhill for Hong Kong from there.
Khaleel Ahmed picked the wicket of Nizakat Khan on 92 in the next over, and went on to pick two more wickets as Indian bowlers razed through the middle and lower order in a 26-run win for India. Yuzvendra Chahal also picked three wickets.