Bare-chested English and Russian supporters hurled bistro chairs and bottles in the historic Vieux-Port district where the cobbled streets were littered with broken glass and debris.
The air was thick with tear gas.
At least five people were hurt in the violence which erupted after massed ranks of fans had been drinking for hours in the southern city.
AFP journalists saw one man with a heavily bloodied face receiving treatment after apparently suffering a cardiac arrest.
Police fired volleys of teargas to disperse the brawling fans as well as local youths who became involved.
Fans were seen marauding through streets throwing chairs and taunting each other.
Six people were arrested, adding to seven arrests in the district on Friday night in similar disturbances.
Police also broke up fighting involving England fans on Thursday.
England fans said the latest clashes were caused by Russians who charged at them.
“There were about 100 Russians, they just came out of nowhere, something was thrown and that started it all off,” said one England supporter who asked not to be named.
Another fan, Danny Hart, 23, said the 9:00 pm (1900 GMT) kickoff time had fuelled the violence.
“I don't think it's a good idea to have scheduled the match at nine o'clock tonight.
“By that time everyone's going to be completely pissed (drunk).”
The England-Russian game was one of five classified as “high-risk” for hooliganism by organisers.
Marseille residents said the violence should have been expected.
“It's the English, what do you expect? We know what it's going to be like when they come here,” said Laurent Ferrero, a pizzeria owner.
“In 1998 it was the same thing,” he said, recalling clashes between English and Tunisian fans in the port city during that year's World Cup.
In Lyon, meanwhile, four French men aged between 20 and 24 were briefly detained following a drunken fight in a bar where England fans had been drinking, police said.
Witnesses said the French men attacked the England supporters. Police did not comment.
The violence has marred French joy at an otherwise smooth start to the giant tournament which has been overshadowed by months of industrial unrest and terror fears.
The host country was boosted by a 2-1 win against Romania in an opening match.