The Brighton game mirrors last seasons opening fixture when on that day Crewe beat the Seagulls 2-1.
The Alex look to have a stern test to the forthcoming campaign with away trips to Carlisle, Hereford and Leeds United.
The local derby for this season is against newly promoted Stockport County and the Railwaymen will lock horns with them in November at home and then in April with it being Crewe's last away game of the season.
Crewe will entertain Oldham Athletic on Boxing Day and will looking to avenge the 4-1 defeat given to them at the end of last season.
While the last game of the season sees Crewe take on Leicester City on 2nd May.