Ireland were skittled out at a 109-run defeat that leaves them 21 down.
After dismissing the Afghans to get 223 the Irish were at a position.
Ireland were making adequate progress on 82-4 earlier a meltdown that saw six wickets fall for 32 runs with Aftab Alam.
The sides match on Sunday in the last ODI in Dehradun.
Afghanistan won the series 3-0 along with their sole defeat to the Irish came on Tuesday.
These were fighting with 81-6 earlier a 50-run partnership between Asghar Afghan (54) and Mohammed Nabi (6 4 ).
Nabi then united with Rashid Khan (52) to get a priceless eighth-wicket rack of 86 until the innings came to a end with five balls to spare.
Andy McBrine (2-37) Boyd Rankin (2-50) both picked up two wickets while the Irish were set a small target.
But, it established well beyond them despite an opening stand of 31 between captain William Porterfield (2-1 ) and Paul Stirling (1-1 ).
Simi Singh hit 20 and Kevin O’Brien top-scored for its Irish with 26 before the wickets tumbled along with also the Irish were out in 35.3 overs.
Alam was ably assisted by Rashid Khan (2-22) and Mujeeb Ur Rahman (2-25) within a extraordinary display from the Afghan bowlers.
“Coming into the game we were really happy where we were at,” explained Ireland captain William Porterfield.
“But today quite a couple of individual errors cost us with the bat in that chase – if we are able to negate some of those we put ourselves at a decent position in the future home strong.”