The bearded midfielder ran 56 metres before unleashing a shot from outside the box which flew into the bottom corner of the net at the 85,000-seat Borg El Arab Stadium.
ymen Hefny, Bassem Morsy and substitute Mostafa Fathy, from a penalty kick, were the other scorers for the five-time African champions, who led 2-0 at half-time.
Zamalek were unrecognisable from the team that failed to impress in the group stage of the premier African club football competition and lost at home and away against Mamelodi Sundowns of South Africa.
The Egyptians played at a fast pace, passed intelligently, finished clinically and goalkeeper Ahmed El Shenawy excelled during the second half as Wydad sought an away goal.
A blunder by Senegal-born Wydad centre-back Mourtada Fall led to the second Zamalek goal on 18 minutes.
He failed to control a back pass and Hefny gained possession before scoring with a low shot into the corner past the outstretched hand of goalkeeper Mohamed Akid.
Rattled Wydad, who won the competition 24 years ago, fell further behind four minutes into the second half and this time Shikabala turned architect.
He floated a free-kick into the heart of the goalmouth and Morsy got to the ball before Akid and a defender and nodded into the net.
A disastrous night for Wydad was completed on 73 minutes when Akid fouled livewire Fathy, who sent the goalkeeper the wrong way from the spot-kick as he tucked the ball into the corner.
It was a record Champions League semi-final winning margin for Zamalek, bettering the 3-0 home triumph over JET (now JS Kabylie) of Algeria in 1984.
ZESCO United of Zambia host Sundowns Saturday at Levy Mwanawasa Stadium in Ndola in the first leg of the other semi-final.