Lord Rose said he would "think twice" about building an empire of high street chains amid a seismic shift in retailing following the rise of online shopping and competition from the likes of Amazon.
He told the Press Association that Sports Direct founder Mr Ashley's strategy risked leaving his empire inflexible in a fast-changing market.
The former chairman and chief executive of retail giant M&S said: "My view in retail is to stay nimble, lean and mean. You need to be able to turn on a sixpence.
"I wouldn't want to lock myself into anything that's not flexible - we're operating in a fast-moving world."
His comments come after Mr Ashley's most recent attempt to expand his burgeoning empire hit the rocks, dealing a blow to his reputation as a shrewd deal-maker.
His attempt to snap up struggling Debenhams ended in embarrassment as the chain was instead placed into administration and Mr Ashley's near 30% stake was wiped out.
He has also become embroiled in a tussle to take over online retailer and school resource supplier Findel.
The Newcastle United owner has been on a buying spree over the past year, most recently adding online player Sofa.com to his stable, having already bought struggling chains including House of Fraser and bike specialist Evans Cycles.
Patisserie Valerie, HMV and LK Bennett also caught the tycoon's fancy, but ended up in other hands.
Having started off in the sportswear market, his business interests now span department stores, gyms and furniture - typically through Sports Direct.
But Lord Rose - who is now chairman of a number of firms, including online grocer Ocado and clothing chains Fat Face and Oasis - suggests Mr Ashley may have had a lucky escape with Debenhams, which he said has "always been behind the curve".
He said: "What we've still got in most sectors in the UK is too much capacity in terms of bricks and mortar.
"Unless you've got a really strong brand or unique selling point, you're going to find you're squeezed. That's why the Debenhams of this world are struggling, that's why BHS disappeared."