With wealthy owners keen to buy success by pumping massive amounts into buying top players, accounts from 665 clubs reveal 56 per cent lost money in the 2010 financial year, and their total debt was €8.4 billion ($10.9 billion).
UEFA general secretary Gianni Infantino said it was "a last wake-up call" for clubs, who have been subject to UEFA's financial fair play monitoring since July 2011.
"We must end this negative spiral and gamble for success," Infantino told reporters at a briefing.
UEFA's top lawyer said it invested "huge" political capital with European institutions to create the fair-play scheme, and that the governing body would not hesitate to enforce the plan's toughest penalty of barring noncompliant clubs from the lucrative Champions League.
"The system is not going to have much credibility if a club ... in serious breach of rules is not sanctioned in an effective way," legal director Alasdair Bell said.
Amid a debt crisis in European economies, Bell said it was "part of the zeitgeist" to promote financial stability.
UEFA's study showed the combined annual loss of top-tier clubs rose 36 per cent, about €400 million ($520 million), compared to 2009.
The losses can be blamed largely on overspending on salaries, staff costs and transfers, as the overall revenue for European top-tier clubs has soared by 42 per cent between 2006 and 2010.
That trend seems to have continued, as Germany's Bundesliga announced Wednesday that 36 clubs in two divisions shared record turnover of €2.23 billion ($2.89 billion) last season.
The 18 top-tier clubs earned a combined €52.5 million ($68 million) in profits, after agreeing to cost-cutting measures in August 2010 which have reduced overall debt to €594 million ($769 million), the league's chief executive Christian Seifert said.
UEFA's research showed that the top five leagues — England, France, Germany, Italy and Spain — has two-thirds of the wealth.
However, richer and more successful clubs were also more likely to lose money.
Of more than 200 clubs playing in UEFA's Champions League and Europa League competitions two years ago, 65 per cent spent more than they earned.
Three out of every four clubs earning more than €50 million ($65 million) annually also recorded a loss.
"Clubs tend to spend more in order to obtain a competitive advantage," said Andrea Traverso, the head of UEFA's financial fair play project.
UEFA outlined a range of sanctions to punish clubs who overspend in an initial two-year monitoring period from 2011-13, or fail to pay wages, transfer fees or social taxes.
UEFA could withhold Champions League and Europa League prize money, deduct group-stage points or prevent new players being registered in its club competitions.
Financial fair play rules allow clubs to make a total loss of €5 million ($6.5 million) in the first assessment period, or up to €45 million ($58 million) if a wealthy owner makes a one-off donation to wipe out losses. UEFA will phase in tighter monitoring rules in future years.
UEFA acknowledged that 13 clubs, including several from England, would have failed its break-even tests on their 2010 accounts. The clubs were not identified but likely included Manchester City and Chelsea, which are bankrolled by wealthy owners.
A total of 31 clubs, including four this season, have been refused entry to its two main club competitions since financial licensing was introduced in 2004.
However, clubs barred this season were from the small-market leagues of Ireland, Kazakhstan, Lithuania and Romania.
Skepticism has grown over UEFA's willingness to take on big-spending clubs such as Premier League leader Man City, whose owners from Abu Dhabi funded a 194.9-million-pound (then $318 million) loss for 2010-11 before monitoring took effect.
"I expect that, at the last moment, (big clubs) will respect the rules," Inter Milan chief executive Ernesto Paolillo said on the sidelines of the briefing. "I can't imagine they would not."
French league leader Paris Saint-Germain spent €82 million ($107 million) on players last off-season after being bought by Qatari owners.
UEFA's project was backed by Jean-Michel Aulas, the president of Lyon whose standing in France is threatened by PSG's revival.
Aulas described a "dichotomy" between clubs spending "easy money and money for investment."
"Tomorrow's paradigm (for clubs) must be built on building stadiums and building youth academies — tangible assets that can benefit football in general," Aulas said.