The 31-year-old opened his account for the club with a double in the league at Bournemouth seven days earlier and followed up with his first goal at Boundary Park to give the Latics a deserved win.
Oldham had an early escape but they went on to dominate the tie and could have won by a bigger margin.
Crewe are above them in the League One Table and recently enjoyed a superb run of five victories in six games but the visitors offered little in attack either side of Hughes' goal.
Match-winner Hughes was a controversial signing by Oldham as he joined them early in the season after spending three years in prison for causing death by dangerous driving.
But Boundary Park manager John Sheridan said: "Lee took his goal well and he is getting better all the time. I always said he would need plenty of games."
Crewe's best chance of the match came in the first minute after Oldham's centre-backs, Stefan Stam and Reuben Hazell, had a misunderstanding 30 yards from their own goal.
Ryan Lowe advanced into the box but fired wide from a great position and it proved a costly miss as Oldham shut up shop and gave them very little joy.
The home side went close through Neil Kilkenny in the eighth minute when he tried his luck from distance and forced Ben Williams to save at the foot of the post.
Williams denied Dean Smalley and had a stroke of luck when Hazell's header from a set-piece cannoned into Craig Davies and flew over the bar.
There was another opening for Gary McDonald before Oldham went in front after 41 minutes as Kilkenny headed forwards and Hughes volleyed in from six yards.
The second half was quiet in comparison and Crewe only threatened an equaliser in the closing stages when there was a scramble in the Oldham box, but no shot on goal at the end of it.