The Irish airline will be jetting off from Hamburg Airport to Lisbon once a week and Porto three times per week, it announced in a statement.
About 150,000 passengers per year will hop on board the return route, with tickets beginning at €24.99 a person, estimated German marketing manager Colm 'O Shea.
The airline is in turn scrapping its flights from the insolvent Lübeck airport, previously its only other northern German hub situated about 90 minutes from Hamburg.
Lübeck Airport was declared insolvent earlier this year and has been bought by Chinese investors.
Ryanair currently operates out of 13 airports in Germany, including Berlin's Schönefeld. In Hamburg, it will compete with four other budget carriers.
Last year, Ryanair CEO Michael O' Leary announced that the low-cost carrier would be soon be expanding to five or six new German airports.
Ryanair's rival Easyjet opened a base in Hamburg earlier this year.