Spread out over 40 cities, nearly 50 thousand people rose in the capital city Bratislava alone, demanding an independent inquiry into the murder of journalist Jan Kuciak and his fiancé Martina Kusznirova.
Mr Kuciak and his wife-to-be, both 27, were found shot dead in their Bratislava home on February 25.
Police have said the couple’s death was most likely linked to Mr Kuciak’s investigation of ties between the Italian mafia and Slovakia’s corrupt politicians.
Peter Nagy, one of the organisers behind the widespread demonstrations, said the time had come for change.
Speaking to Polish Radio, he said: “First of all we need a new Government.
“A Government which is not corrupt, without links to the mafia and will have the support of the people.
Slovakia protests: The murder of a journalist triggered widespread demonstrations
“We think there are politicians in Slovakia who can represent the voice of the protesters.”
First of all we need a new Government
Those attending the fierce anti-Government protests in Bratislava, jingled their keys in unison, harking back to the 1989 Velvet revolution.
Maria Kuciak, the murdered journalist’s sister thanked the gathered crowds for not being indifferent in the face of recent events.
Many protesters said they have been “frustrated too long, are willing to change things, and can no longer stay silent”.
Slovakia protests: At least 50 thousand people took to the streets of Bratislava
Slovakia protest: Protestors demand the Government resigns from office
Maria Kuliovska, 30, who attended the march said: “Politicians in power have lost our trust.
“We don’t trust them to guarantee an independent investigation. They have failed to investigate all previous scandals.”
Under Mr Fico, who has been in power for a decade, the Slovak economy has flourished but he now appears to be on borrowed time.
President Andrej Kiska, a political rival of the Prime Minster, said his country is suffering a crisis of trust and called for an early election.
Slovakia protests: The murder of Jan Kuciak and his fiance sparked the outrage
Slovakia protests: Local media estimate 1.8 percent of the country took part
Parliamentary speaker Andrej Danko, one of the country’s three highest ranking officials, urged his nation to remain calm.
He said: “We want society to remain peaceful and calm and Slovakia’s top three officials will do their best to prevent the events of recent days from being politically exploited.”
So far no-one has been charged with the murder of Mr Kuciak and his fiancé.
Two locals activists, Juraj Szeliga i Karolina Farska, said their country has never been shaken to this degree.
Slovakia protests: Protesters demand an independent inquiry into the murders
The pair said: “Over the past days Slovakia has been shaken in a way it has not in a long time.
“We want to stand behind an honest and democratic country.
By some local media estimates, around 1.8 percent of the country’s population actively took part in the demonstrations.