The 20-year-old Commonwealth Games silver medallist, who toured Australia with England earlier this summer, will undergo surgery to repair a slight cartilage tear.
He might miss Newcastle's opening five Guinness Premiership games as a result, although the Falcons are confident of him making a full and quick recovery.
"Mathew has a slight cartilage tear which hasn't settled down," said Newcastle rugby director John Fletcher, ahead of Sunday's Premiership opener at Northampton.
"He will have an operation to tidy that up, and we are probably looking at four to six weeks (out).
"He could have actually played this weekend - the injury isn't that bad -but it is in an awkward place on his knee and he may well have been playing in pain until it was sorted out.
"So we have made the decision to operate and get it out of the equation altogether."
Tait, a high-class centre or wing, is likely to feature in England boss Andy Robinson's autumn Test plans, as should 2003 World Cup hero Jonny Wilkinson, who will start the season on schedule following his well-chronicled injury problems.
Wilkinson will be partnered at half-back by Hall Charlton against the Saints, and his head-to-head with Northampton fly-half Carlos Spencer promises to provide a fascinating opening weekend highlight.