Figures released by European football's governing body revealed that clubs lost more than 1.6billion euros (£1.33billion) in 2010 - a 36% increase and the worst statistics on record.
A survey of 665 clubs found that 56% posted losses in the 2010 financial year, with 78 spending more than 100% of their income on wages.
UEFA general secretary Gianni Infantino revealed that only four leagues of the top 30 clubs in Europe were currently living within their means.
He told a briefing in Nyon: "This is the last wake-up call for everyone, this trend has to change very quickly to safeguard European football.
"We must end this negative spiral and gamble for success. These losses cannot continue."
Under UEFA rules, clubs are allowed to make a maximum loss of 45million euros (£37.5million) over a two-year rolling period, followed by 30 million euros (£25million) for three years - moving ultimately towards breaking even.
But UEFA revealed that 13 clubs monitored in the 2010 financial year would have failed the break-even tests if the rules were applied now.
Warning that it would not put up with permanent losses, UEFA pointed out that 31 clubs, including four this season, have already been refused entry to its two main club competitions since financial licensing was introduced in 2004.
Lyon president Jean-Michel Aulas said there had to be a distinction between clubs spending "easy money, and money for investment".
He explained: "Tomorrow's model must be built on building stadiums and building youth academies - tangible assets that can benefit football in general."
Ernesto Paolillo, chief executive officer of Inter Milan, compared the situation to the economic meltdowns affecting the Eurozone.
He said: "I can compare the situation of the football industry to exactly the situation of Italy, Spain and Greece's balance sheet."
Infantino said clubs that breach the rules could be ordered to cut their squads for European competitions if they keep buying players while incurring unacceptable losses.
UEFA could also deduct points from teams as well as impose fines and, ultimately, exclude them from European competition depending on the severity of the infringement.
UEFA's head of legal affairs, Alistair Bell, said detailed talks had already been held with European authorities to make sure the rules had bite.
HE said: "The system is not going to have much credibility if a big club that is in serious breach of the rules is not punished in an effective way.
"For me the sanctions need to be effective enough that people come into compliance with the system, otherwise clubs are going to become disillusioned rapidly."