The hosts, beaten 2-0 in the recent T20 series, were chasing a target of 228 to win but were bowled out for 198.
Having slipped to 93 for four, Ireland were relying on Andy Balbirnie, but when he fell for a gritty 55 their hopes evaporated.
Earlier, Ireland's bowlers had restricted Afghanistan to 227 for nine.
Gulbadin Naib top scored with 64 and shared a fourth-wicket partnership of 77 with Hashmatullah Shahidi, who hit 54.
First Published: August 27, 2018, 11:25 PM IST