Scotland's two most recent qualifiers saw them manage just one point in games against Lithuania and Slovakia, after a 5-1 win over Malta in their opening group match.
The Scots lost 3-2 on their last visit to Wembley in a 2013 friendly and won 1-0 there in their last competitive match, only to lose 2-1 on aggregate in a Euro 2000 play-off.
"I think they have to win it, but that's not a problem, they can win it," said Ferguson, 74, speaking in his native Glasgow to highlight Hampden Park's status as a Euro 2020 host stadium.
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The former Manchester United said, "If you go back to the European Championship a few years ago, they went down there and were very, very unlucky. In the last minute I think it was (Christian) Dailly who had the header that was saved by (David) Seaman. They'll do well Scotland, they will be fine."
Scotland's ticket allocation of 13,700 for the Wembley showdown on November 11 sold out quickly but Ferguson believes even more travelling fans will be in London.
"Scotland always do well against England," he said.
"It's always a great incentive, the underdog. And the support will be fantastic -- whatever they allocate Scotland it will be treble that. They will find tickets somewhere," added the 74-year-old, who was Scotland's manager at the 1986 World Cup in Mexico following the death of Jock Stein.
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Ferguson said his favourite memory from international football's oldest fixture concerned Scotland's 3-2 win at Wembley against an England side that only the year before, in 1966, had won the World Cup.
Jim Baxter and Denis Law starred in a famous Scotland win and Ferguson said: "I was originally in the squad when Denis had a knee injury. But he was fit.
"My dad had never been to Wembley and he booked tickets because I was in the squad at the time. To win 3-2 was fantastic."
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