Emirates will deploy an A380 on its Frankfurt route from September.
The Gulf carrier currently serves the German city with a triple-daily B777 operation.
From September 1, flight EK45 and return service EK46 will become a superjumbo service seating 519 passengers.
EK45 departs Dubai at 0825 and arrives in Frankfurt at 1315 local time, while EK46 will takes off from Frankfurt at 1520 and lands in Dubai at 2335 local time.
Thierry Antinori, Emirates ' executive vice president and CCO, said: "Frankfurt was one of the first European destinations for Emirates and as the financial capital of Germany it continues to be strategically important.
"Deploying larger capacity aircraft, such as the A380, is central to helping us meet growing passenger demand between one of the Europe's busiest economic regions and the emerging economies of Asia, Middle East and Africa, through seamless, swift connections via our Dubai hub."
Emirates also operates a double-daily A380 service to Munich.
The airline has 48 A380s in its fleet and is the largest global operator of the superjumbo.
Last week, Emirates flew an A380 to Vienna in a one-off move that might be a prelude to it inaugurating a regular superjumbo service to the city (see news, May 27).