Andy McBrine and Lorcan Tucker both produced career-best performances for Ireland, but the side could not recover from two dropped catches and a missed run-out and handed Afghanistan their first 10 points in the World Cup Super League.
The final margin was just 16 runs but Ireland could not match Rashid Khan's devastating 35-ball 55 which propelled his side to 287-9, as Afghanistan plundered 66 from the last five overs.
Crucially, a more accurate throw from Harry Tector would have left Rashid stranded when he had scored just five and then Tucker dropped him behind the stumps on 37.
The other 'big miss' was also by Tucker when Rahmanullah Gurbaz was 19; the teenage one-day international debutant went on to score 127, the second highest by anyone in their first ODI.
To Tucker's credit, he showed tremendous resilience and character to come back strong with the bat to hit 83, comfortably Ireland's top score on the day, and Andrew Balbirnie admitted that was where the match was lost.
"The top order needs to be more consistent," said the Ireland skipper. "A number of us got starts, including myself, but while we got out in the 20s and 30s, they had a player who went on and got a hundred and that was the difference.
"But some of our guys are still finding their feet in international cricket and can take a lot of positives. To score 270 (batting second) on that wicket was good but not enough to win the game today. We know the areas where we could have done better but it is exciting to see this group learn and improve every day.
"Andy bowled brilliantly, was incredibly accurate and completely deserved his five-wicket haul on a pitch that offered spin."
McBrine, the North West Warriors captain, had never taken more than three wickets in an innings before in 83 matches across all formats but, much like Simi Singh against UAE last Monday, this was his day.
The Donemana off-spinner broke the opening partnership of 120 in his fifth over, Javed Ahmedi holing out to deep mid-wicket, and finished his spell with four more in his last 22 balls, the last three caught at leg slip by Kevin O'Brien as the batsmen failed to cope with the turning ball.
Gurbaz, however, could not be removed until the 38th over, another catch by Singh in the deep in an innings which included eight fours and nine sixes (Ireland cleared the boundary only four times in their 50 overs to Afghanistan's total of 17). Rashid hit five maximums, two of them in the final over off Barry McCarthy, after the dropped catch.
Encouragingly for Ireland going into the remaining two games, the fastest bowler to 100 wickets in ODIs was restricted to two yesterday at a cost of 56 runs but the main damage was done before he entered the attack in the 21st over; Ireland were 98-4.