"After the enormous Beirut catastrophe, I announce my resignation from government," she said in a statement carried by local media, apologising to the Lebanese public for failing them.
The head of Lebanon's Maronite church meanwhile called on the entire government to step down over the August 4 explosion, a blast widely seen as shocking proof of the rot at the core of the state apparatus.
Lebanese protesters enraged by the blast vowed to rally again after a night of street clashes in which they stormed several ministries.
Maronite patriarch Beshara Rai joined the chorus of people pressing Prime Minister Hassan Diab's cabinet to step down over a blast he said could be "described as a crime against humanity."
"It is not enough for a lawmaker to resign here or a minister to resign there," Rai said in a Sunday sermon.
"It is necessary, out of sensitivity to the feelings of the Lebanese and the immense responsibility required, for the entire government to resign, because it is incapable of moving the country forward."
Read also: Lebanon PM Diab to call for early polls after deadly blast
Rai echoed calls by Diab for early parliamentary polls - a long-standing demand of a protest movement that began in October, demanding the removal of a policial class deemed inept and corrupt.
He also joined world leaders, international organisations and the angry Lebanese public by pressing for an international probe into an explosion authorities say was triggered by a fire in a port warehouse, where a huge shipment of hazardous ammonium nitrate had languished for years.
President Michel Aoun on Friday rejected calls for an international investigation, which he said would "dilute the truth."
At least six lawmakers have quit since the explosion.
Under increased pressure from the street and foreign partners exasperated by the leadership's inability to enact reforms, Diab's government is fraying at the edges.
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