The maiden Test win for Ireland came in their 8th game in the traditional format.
Captain Andy Balbirnie led from the front with an undefeated 58 as Ireland won the one-off Test by 6 wickets in the final session on the third day, successfully chasing down a modest target of 111.
Ireland had played their first Test back in 2018 when they were defeated by Pakistan.
Afghanistan resumed their second innings Friday on 134-3 before they were dismissed for 218.
Skipper Hashmatullah Shahidi top scored with 55 while Rahmanullah Gurbaz, making his Test debut, hit 46.
Mark Adair picked up three wickets to finish with eight for the match. Craig Young and Barry McCarthy also claimed three apiece.
Gurbaz, better known for his flamboyant and explosive shot-making in limited overs cricket, clubbed the only two sixes of the innings.
Chasing just 111 for victory, Ireland slumped to 13-3 with 18-year-old fast bowler Naveed Zadran clean-bowling opener Peter Moor and Curtis Campher, both without scoring.
Balbirnie denied the teenager a hat-trick but Harry Tector was soon caught behind by Gurbaz off Nijat Masood for two.
Balbirnie and Paul Stirling, who both played in Ireland’s debut Test in 2018, briefly steadied dressing room nerves.
Stirling was then caught in the slips off left-arm spinner Zia-ur-Rehman for 14 as Ireland slipped to 39-4 just after tea.
However, Balbirnie moved watchfully to his fourth Test half-century, which came from 86 balls, ably supported by Lorcan Tucker (27 not out) in a crucial winning partnership of 72.
The two teams will now play three one-day internationals and three T20 games as part of their multi-format series.
(With inputs from AFP)