The criminal organisation forged the animals' identification by modifying theirs microchips and documentation, Europol alleges.
They worked in co-ordination with Belgium, France, Italy, Portugal, Romania, Switzerland and the UK, Europol said in a statement.
Of the 66 people arrested, 65 were arrested by Spanish police with the other person being arrested in Belgium.
The 2013 horsemeat scandal resulted in meat products being pulled from supermarket shelves across several countries, including Ireland and the UK.
A total of 65 people have been arrested and charged in Spain, with charges including animal abuse, money laundering and crimes against public health.
Horse DNA was discovered in frozen beef burgers sold in a number of British and Irish supermarkets in 2013.
As per investigative agencies, the meat was not fit for human consumption.
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The leader of the criminal group, a Dutch national, was arrested in Belgium as part of the operation, but Europol believe that the Spanish group is just a small part of his overall trading reach.
Spain's Guardia Civil (police) began Operation Gazel a year ago after detecting unusual behaviour in horsemeat markets.
According to Europol, the Dutchman had put "his most trusted men in charge in every country affected by the scam".
"The investigation revealed the existence of an organization which acquired horses which were in bad condition and old and not apt for consumption and sacrificed them in two specific slaughter houses", a spokesman for the Civil Guard added. This action was coordinated by the Federal Police, the Federal Food Agency in Belgium and Guardia Civil.
Police carried out raids in both Alicante and Leon, in the north of Spain, blocking or seizing bank accounts and properties, and confiscating five luxury cars.
European Union police coordinating organization Europol announced Sunday that eight nations cooperated in the operation. The results concluded that the destination of the horse meat was mainly outside of Spain, due to the fact that the samples in Spain matched those found overseas.