Twice world champions South Africa are the favourites but as they learned in their shock defeat by Japan in their opening game that upsets can happen.
They need a victory to ensure they will not be flying home early and bonus points would be handy too.
Scotland top the group with maximum points from wins over Japan and the United States. Marshalled by captain Greig Laidlaw, they can be expected to play with their trademark tenacity.
Defeat would still leave the Scots with a chance of qualifying provided they beat Samoa in their final pool game, not necessarily an easy task.
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A win should put them through to the quarter-finals for the first time since the 2007 tournament, barring an unlikely points permutation.
The 'Fog on the Tyne' tune greeted the crowds of green-clad Springboks fans spilling out of the trains running up from London to this northern English city.
Scots have marched south over the border in big numbers too, strolling Newcastle's streets in kilts and navy blue rugby shirts before the game as bag-pipers played.
"I think we'll edge it. I think South Africa will crumble," said Scotland supporter Stuart Argyll, a business analyst.
"We've been playing well in the second half of every game."
Gail Nicholl-Stout, from Haddington, near Edinburgh, was less confident.
"I'd like to think Scotland are going to win, We've had two good games already," she said, dressed in a tartan miniskirt and sporting a Glengarry cap bedecked with a long feather.
"There's certainly going to be a lot of support today."
On the train north, Springbok fans Perry Rungunsanay and Zander Van Houpen, bankers from Johannesburg, were optimistic.
"We had a good wake-up from Japan. We underestimated them. We won't underestimate Scotland. Scotland will go for it," Van Houpen said.
Perry was under no doubt the powerful Springboks would take care of business.
"We'll win comfortably," he said. "It's a new captain and a lot of players will play for him. They are also playing for places in the team in the next round."
The Scots are missing sparky flyhalf Finn Russell, the 23-year-old playmaker replaced by Duncan Weir among Cotter's 10 changes from the side that beat the United States.
The two sides first met in 1906. South Africa have won four of their past five meetings, the most recent being last year's 55-6 drubbing in Port Elizabeth.
(Editing by Ed Osmond)
