The Irish Sun says the odds on Wazza heading to Spain were slashed from 40/1 to 5/1 after a flurry of large bets.
The move prompted rumours Rooney may be offered by United to Madrid as part of a deal to re-sign Portuguese superstar Ronaldo.
Ladbrokes spokesman Alex Donohue said: “From nowhere there has been a big gamble on Rooney to Real Madrid.
“A series of people have asked for the maximum stake bet — which means they have walked into a shop and said, ‘I want to put the maximum I can on Rooney going to Madrid’.
“The gamble shows no sign of stopping and if it proves to be more than just a rumour, we’ll be paying out plenty.”
He added: “It’s rare to see a run of money for something which hasn’t been widely reported in the papers or on the internet.”
Last month the first indication that David Moyes was taking over from Sir Alex Ferguson at Old Trafford came when bookies slashed his odds.