Europol said a five-country probe had identified some 380 suspicious matches targeted by a Singapore-based betting cartel, whose illegal activities stretched to players, referees and officials across the world and at all levels of the game.
Matches included two Champions League games, one of them in England and World Cup qualifiers, netting criminals more than eight million euros ($US11 million, 6.9 million pounds) in profit.
"It is clear to us that this is the biggest investigation ever into suspected match-fixing," Europol director Rob Wainwright told a news conference in The Hague, adding that the fall-out hit at the heart of the world game's reputation.
"It is the work of a sophisticated organised crime syndicate based in Asia and working with criminal facilitators around Europe.
"Match-fixing is a significant threat to football, involving a broad community of actors. Illegal profits are being made that threatens the very fabric of the game."
World governing body FIFA said closer cooperation was needed between football's authorities and law enforcement agencies to crack down on match-fixers.
"FIFA and the football community are committed to tackling this problem, but we will not succeed alone," said FIFA's own "corruption buster" Ralph Mutschke, a former Interpol executive and police officer.
"The support of law enforcement bodies, legal investigations and ultimately tougher sanctions are required, as currently there is low risk and high gain potential for the fixers."
European governing body UEFA for its part said it was already working with the authorities "on these serious matters as part of its zero tolerance policy towards match-fixing in our sport.
"Once the details of these investigations are in UEFA's hands, then they will be reviewed by the appropriate disciplinary bodies in order that the necessary measures are taken," it added in a statement.
The global policing body's chief Ronald Noble said last November it expected to make arrests in Singapore over last year's Italian illegal betting scandal after links were suspected between one suspect and crimelord Tan Seet Eng or Dan Tan.
As part of investigations, which involved investigators in Germany, Hungary, Slovenia, Finland and Austria, 14 people have already been sentenced to a total of 39 years in prison, Europol said, with more than 100 prosecutions still expected.
At least 425 referees, players and other officials were suspected of involvement, with matches rigged so that major sums of money could be won through betting.
Some 151 suspects were living in Germany, 66 in Turkey and 29 in Switzerland but suspects fixing matches in other parts of Europe and around the world are also being probed, Europol said.
No details were given about which top-flight matches were involved because some investigations were still on-going.
But footage was shown of a suspect junior international between Argentina and Bolivia during which a Hungarian referee awarded a highly dubious penalty in extra time.
The largest bet profit was 700,000 euros in an Austrian league match between Redbull Salzburg and Hartberg. As well as arrests, some two million euros in cash and profits were seized, Europol said.
A further 300 suspicious matches were identified outside Europe in Africa, Asia and South and Central America.