A flotilla carrying humanitarian aid and activists, including Swedish climate campaigner Greta Thunberg, set sail to Gaza from Barcelona on Sunday.
The vessels left from the Spanish city to try to "break the illegal siege of Gaza", the organisers said. They did not specify the number of ships involved or the exact departure time.
The flotilla is expected to arrive in the waters of the war-ravaged Gaza Strip in mid-September.
Organisers said other vessels were expected to leave Tunisia and other Mediterranean ports on September 4.
Activists will also stage simultaneous demonstrations and other protests in 44 countries "in solidarity with the Palestinian people", Ms Thunberg wrote on Instagram.
The flotilla will include activists from several countries, European lawmakers and public figures, such as former Barcelona mayor Ada Colau.
Israel blocked all aid to Gaza in March. A limited amount began entering in May, with food now being distributed by a private US foundation whose operations have been marred by violence. Limited supplies have resumed, as well as air aid drops, but these are far from sufficient amid mass starvation and famine.
Israel has already prevented two attempts by activists to deliver aid by ship to Gaza this year.
In June, 12 activists on board the sailboat Madleen, from France, Germany, Brazil, Turkey, Sweden, Spain and the Netherlands, were intercepted by Israeli forces 185km from Gaza. The passengers, including Ms Thunberg, were detained and expelled.
In July, 21 activists from 10 countries were intercepted as they tried to approach Gaza in another vessel, the Handala.
The humanitarian situation has continued to rapidly deteriorate since, culminating in the UN declaring a state of famine in the enclave.
An Israeli official told the AP on Saturday that Israel will soon slow or halt humanitarian aid into Gaza as it expands its war on the enclave. The official, speaking on condition of anonymity, said Israel would stop airdrops over Gaza city in the coming days and reduce lorries as it prepares to push hundreds of thousands of people to the south.
Residents of Gaza city have repeatedly said they refuse to leave.
