After losing to Bermuda in their qualifying series opener, the Saltires desperately needed a victory to get their bid back on track but a second loss at the Sharjah Cricket Stadium leaves them facing an uphill struggle.
Despite seeing Calum MacLeod (56) and Matt Machan (54) both land half-centuries, Scotland could only fight their way to 154 for six from their 20 overs, leaving them well short of the Afghans' target of 172.
Afghanistan won the toss and decided to bat as they put the pressure on their opponents with decent knocks by skipper Mohammad Nabi (46) and Mohammad Shahzad (42).
Samiullah Shenwari also contributed with his score of 31 as the Scots' bowling attack failed to dent the wave of Afghan runs.
Only Iain Wardlaw took wickets with any regularity as he finished with figures of three for 40.
In reply, the Scots overcame the loss of opener Richie Berrington for just 19 runs as MacLeod and Machan ran up decent scores but captain Kyle Coetzer, Rob Taylor, Safyaan Sharif, Gordon Goudie and David Murphy all fell cheaply as a second defeat was confirmed.
All is not lost for Coetzer's side, however, with six countries still to qualify for the expanded 16-team World Twenty20 tournament but they must do better against Kenya in Dubai on Tuesday.