Nearly 8,000 people from 39 countries have been arrested this month in the US.
The move was described by the US Immigration and Naturalisation Service as its largest international anti-smuggling operation ever.
The three-week sting involved law enforcement agencies in the United States, Canada and 12 Latin American and Caribbean countries.
"Operation Crossroads International provides us very important lessons about one of the great, great problems we have today on human smuggling," said INS Acting Commissioner Kevin Rooney.
"This multibillion-dollar global industry is becoming increasingly sophisticated and is often intertwined with other criminal activities."
Officials said 75 smugglers and vendors of illegal documents were arrested during the operation. Thirty-eight of them face smuggling charges, two in the United States. Fourteen face charges on other immigration related violations. The remaining suspects face other charges.
In 13 cases, officials also seized illegal drugs valued at $9m (£6.35m).
The arrests were largely made through checking of documents at hotels, airports, highway checkpoints and safe houses - where smugglers stored immigrants while moving them - in the other countries.
INS officers also helped some of the countries to check passengers' documents at international airports.