The authorities have called for the removal of the listings almost 66,000 properties from the rental platform as demonstrations against tourists continue across the country - with a protest in the Canary Islands last weekend attracting thousands.
Pablo Bustinduy, the minister for social rights, consumer affairs and the 2030 Agenda, says that the rental properties have "violated various norms regarding housing for tourist use".
The affected properties are in six regions: Madrid, Andalusia, Catalonia, Valencia, the Basque Country and the Balearic Islands.
The announcement comes following a court ruling in the Spanish capital declaring that Airbnb must immediately withdraw the 4,984 properties cited by the ministry from the market.
Bustinduy and the ministry now await further judicial rulings on around 60,000 other properties whose listings have been deemed unlawful.
He described the court's decision as a "clear victory for those who fight to protect the right to housing".
Bustinduy added: "It can be possible to ensure that no economic interest has priority over housing and that no company, however big or powerful, is above the law."
Housing has emerged as a major issue in Spain in recent times and Prime Minister Pedro Sanchez declared earlier this year that "there are too many Airbnbs and not enough homes".
However, the company argues that the housing issue across Spain is a broader problem and putting restrictions on rental properties will not fix anything.
A spokesperson said: "The root cause of the affordable housing crisis in Spain is a lack of supply to meet demand.
"Governments across the world are seeing that regulating Airbnb does not alleviate housing concerns or return homes to the market - it only hurts local families who rely on hosting to afford their homes and rising costs."