Ms de la Vega said the countries of origin should be told that Spain would act "with complete firmness".
Amnesty
"Let me be clear - those who enter Spain illegally, sooner or later they will leave Spain," she told a meeting of Spanish ambassadors.
Foreign Minister Miguel Angel Moratinos said that Spain needed to tighten up its borders, but countries of origin "must facilitate mechanisms of repatriation".
Spain has been criticised by European Commission Vice President Franco Frattini for a 2005 amnesty for 600,000 illegal immigrants, on the grounds that it encourages more people to try to reach Spain.
A poll for Cadena Ser radio on published Monday suggested that immigration now worried Spaniards more than anything else.
The Canary Islands have become one of the main gateways for African migrants, following a crackdown on migration to the north African Spanish enclaves of Ceuta and Melilla in 2005.
The migrants take to the seas crammed into open wooden boats for a crossing of up to 10 days. An unknown number do not make it.
'Maltreatment'
Africans make up only a small proportion of the more than half a million people migrating to Spain every year, but they put strains on the resources of the Canary Islands.
On Monday officials said internment centres which had room for 5,446 people, were already holding 5,461 - while another 700 were being held in police stations.
Thousands of migrants have already been transferred to the mainland this year, and some have been sent home.
Senegal suspended repatriation of its citizens earlier this year, after migrants returned claiming the had been maltreated.
Last week Spain called on the European Union for more help to deal with the crisis.
Experts from several EU countries have been helping identify the nationality of migrants landing in the Canary Islands since July.
Ships from Portugal and Italy and a Finnish aircraft are also supposed to be helping patrol the West African coast.
But Spain says more boats, planes and personnel are needed.