Lesly Jana Emmanuel and Kunarobinson Christhurajah are accused of organizing, inducing and aiding in the operation that brought the Tamils by boat to British Columbia.
The MV Sun Sea landed off Victoria in August 2010 with the refugee claimants on board.
The court indictment against the pair alleges they planned their crimes between August 2009 and August 2010 in Sri Lanka, Malaysia and Thailand.
RCMP Sgt. Duncan Pound said Tuesday that police in Canada were dealing with a vast area as part of their investigation.
"It made it a challenging investigation for the RCMP," he said. "Our federal investigators had to work with international partners, they had to travel. This wasn't a case where we could gather all the evidence here in Canada."
The two accused are expected to appear in a Vancouver provincial court on Wednesday.
The Canadian government has also launched an extradition request for a third man charged with the same crime and arrested in France.
Pound said the RCMP has provided all of its evidence for a charge against Thayakaran Markandu and was working with Canada's Justice Department in the extradition request.
There were 380 men, 63 women and 49 children on board the ship when it came ashore.
Almost two years later, six men from the ship remain in detention and 19 passengers have been issued deportation orders.
The Immigration and Refugee Board said six people have been accepted as refugees, another six have been rejected, one family has abandoned its claim and 18 more claims have been withdrawn.
Pound couldn't say if more people would face charges in connection with the smuggling operation.
"The file remains ongoing and a priority for the RCMP and we'll continue to track that evidence until everyone who should be charged is charged."
The Sun Sea arrived a year after the MV Ocean Lady brought 76 Tamil migrants to the B.C. coast.
Since the two ships arrived, the Canadian government launched an international effort to prevent smugglers from reaching the country's shores.
Prime Minister Stephen Harper gave Thailand another $12 million to combat such smuggling operations when he visited in March.
Harper said at the time that several illegal smuggling operations were blocked and boats were stopped before they could sail to Canada.
The government is also implementing a tough new immigration law that targets such schemes.
The law would allow the immigration minister to designate the refugee claimants as "irregular arrivals" and allow them to be held for up to a year while their identity is checked and their refugee claims are processed.
The government congratulated the Mounties Tuesday for what it called important arrests.
"Human smuggling is a crime that our government takes very seriously," said the joint statement from Public Safety Minister Vic Toews and Immigration Minister Jason Kenny.
The ministers said Canada is a generous and compassionate country that welcomes newcomers, but Canadians aren't naive.
"Canada will not tolerate abuse of our immigration system for financial gain through the despicable crime of human smuggling."