Flight EK017 touched down in Manchester at noon and the return flight is due to land in Dubai on Thursday morning (2 September).
Emirates currently offers daily services to the north west airport, which will increase to a double daily A380 service by October.
The resumption coincides with the 11th anniversary of the Emirates A380 serving the north west, after it was first introduced on 1 September, 2010.
Richard Jewsbury, divisional vice president at Emirates UK, said: "We’re incredibly pleased to see the return of A380 flights to and from Manchester, responding to increased passenger demand.