About 1700 activists set off from the capital Tunis in buses and cars, according to the state news agency TAP, including about 200 from Algeria.
They plan to travel to Egypt's Rafah border crossing with the Gaza Strip, hoping to draw attention to the humanitarian emergency in the sealed-off coastal territory and to protest against Israel's attacks.
The convoy calls on "all free people worldwide" to stand up for Palestinian rights, spokesman Wael Nauar said.
Yahia Sarri, who is co-ordinating the action for Algeria, told DPA: "The time for solidarity on screens is over. We are now moving with peaceful convoys that carry the voices of people around the world."
Activists from Morocco were unable to join as planned.
Disputes over the shared border have existed with Algeria for decades.
The convoy is scheduled to travel through several cities in Tunisia and from there into neighbouring Libya.
It will continue along the Mediterranean coast to Egypt and finally to Rafah.
The border crossing is more than 3000km from Tunis.
The convoy is setting off at the same time as international activists are planning to gather in Egypt this week.
After a meeting in the capital Cairo, they plan to walk about 50km from the coastal town of al-Arish to Rafah on Friday.
The activists plan to demonstrate at the crossing for several days starting on Sunday but it is unclear whether the Egyptian authorities will permit the action.
Meanwhile, a group of activists led by Greta Thunberg has been trying for days to deliver aid to the Gaza Strip via a boat that set sail from Sicily.
However, the Israeli military stopped the ship overnight shortly before it could reach its destination.
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