Ireland almost stumbled when they needed nine runs to win in the super over, but Kevin O'Brien stepped up under pressure.
Mujeeb Ur Rahman claimed 3-38 as Ireland fell short against Afghanistan, who now lead 2-0 with one Twenty20 fixture remaining.
Afghanistan have defeated Ireland in the first T20I after rain stopped play when they were well on their way to a victory target of 173.
Batsman Asghar Afghan has replaced Rashid Khan as Afghanistan captain, having been sacked in April.
West Indies chased down 31 runs with ease after bowling out Afghanistan on Friday morning.
Afghanistan lead West Indies by only 19 runs with just three wickets remaining in their second innings in Lucknow.
Afghanistan squandered a good start to the Test against West Indies as Rahkeem Cornwall picked up seven wickets for just 75 runs.
Nicholas Pooran admitted altering the condition of the ball for West Indies during the third ODI against Afghanistan.
Afghanistan came from 1-0 down to win the Twenty20 international series against West Indies, Rahmanullah Gurbaz starring with the bat.
All-rounder Karim Janat stole the show with incredible figures of 5-11 as Afghanistan made it 1-1 in the three-match T20 series.