Gambia U-17 suffered a 5-1 home defeat to their West African counterparts at the Independence Sports Stadium.
Youngster Nina Norshie snatched the opener for the Black Maidens in the early minutes of the match.
Skipper Abdulai Mukarama netted a hat-trick in the first department of the match before the Gambians pulled one back through Fatoumata Sowe.
Back from the break, In-form Northern Ladies goal poacher Mukarama completed Ghana's victory with another stunning strike.
Coach Evan Adotey's side will host Gambia in the return leg encounter in a fortnight at the Cape Coast Stadium.
The Winner will advance to the next stage of the 2018 FIFA World Cup qualifiers which will be staged in Uruguay.