New boss Steve Rowe said "more than 100 UK stores - a quarter of its UK floorspace - would be affected by the shakeup with clothing departments to be shut entirely in 60 stores."
Another 45 stores will either be turned into branches of its more successful Simply Food chain, downsized or relocated.
The three-year plan, which aims to boost sales as more Britons buy clothing online, is expected to cost 150 million pounds.
He has already promised to lower its clothing prices and pay more attention to its most loyal group of shoppers, dubbed "Mrs M&S".
The troubles at M&S have enabled low-cost rivals such as H&M, Zara and Primark to thrive on the high street.
The strategy update came as the retailer reported a 19 per cent fall in underlying profits before tax to 131.3 million pounds in the six months to October 1, reports said.