Ireland failed to bounce back from their Twenty20 defeats to Afghanistan as they lost the opening one-day international between the sides.
Afghanistan were 2-0 winners in a curtailed T20 series and carried their momentum into Monday's 50-over clash in Belfast, prevailing by 29 runs despite Ireland captain William Porterfield's assurances that his side would be "more confident" in this format.
Gulbadin Naib (64) and Hashmatullah Shahidi (54) led the way as the tourists reached 227-9, with Ireland left relying largely on the efforts of Tim Murtagh (4-31) and Boyd Rankin (3-44).
The home side then fell well short of the run rate required to chase down the visitors and were ultimately bowled out for 198 with nine balls remaining.
Andy Balbirnie (55) was Ireland's most potent threat with the bat, but his team-mates failed to match his level of scoring and back-to-back wickets from Rashid Khan put the match to bed.
Two more ODIs follow at Stormont on Wednesday and Friday, with Ireland needing to win the next to stand a chance of salvaging a series victory.