About 200 people assembled in a car park in Nice, on France's Mediterranean coast, where many showed Canadian flags in recognition of the lorry drivers’ protest in Canada.
They set off from Nice for the 930 kilometre drive to the capital and then hope to complete another 300km drive to Brussels, Belgium, and the headquarters of the EU.
“Lots of people don't understand why a vaccine pass is in force in France,” said Denis, who was helping to co-ordinate the convoy from Nice.
“Our work is to communicate to Europe that putting in place a health pass until 2023 is something the majority of our fellow citizens cannot understand."
In the city of Perpignan, near France's border with Spain, another 200 people set off towards Paris as part of the “freedom convoy” movement.
They want, among other things, an end to rules barring people from public venues if they do not have a Covid vaccination.
The convoy consisted of cars, camper vans and one lorry.
“We are just tired of it all,” said Nicolas Bourrat, an independent lorry driver. "We want to go where we want without being asked for a vaccine pass. At least with this action, I am doing something."
Not everyone setting out from Nice planned to travel all the way to Paris or Brussels.
Meanwhile, Canadian Prime Minister Justin Trudeau has said the lorry driver protests besieging central Ottawa are undermining democracy, and the country's public safety minister has told US Republicans to stay out of Canada's domestic affairs.
Protesters say they will not leave until all vaccine mandates and Covid restrictions are lifted.
The protests began in Ottawa but spread across the country, with lorry blockades halting commercial traffic at critical border crossings, including the Ambassador Bridge into Detroit.
Many members of the US Republican Party, including former president Donald Trump, have made comments supporting the demonstrations.