The EU's executive body dismissed a plea by Spain's foreign minister that Spain's own economic situation and battle to control illegal immigration at its own borders should be further taken into account when determining the quotas.
The quotas were announced by the European Commission in its European Agenda on Migration on Wednesday and will become mandatory once voted in by the Council of Ministers.
Spain will be required to take 4,288 of the 40,000 asylum seekers in Italy and Greece destined to be relocated across EU member-states. The figure represents 10.72 percent of the total, a far cry below Germany at 21.91 percent and France at 16.88 percent.
Spain will also be expected to take in a further 1,549 people over the next two years under the voluntary scheme to settle 20,000 people fleeing conflict who are currently residing outside the EU.
The quota per country is based on a redistribution key that gives population size a weight of 40 percent, with a further 40 percent based on economic growth, 10 percent on unemployment and 10 percent on former engagement with asylum seekers.
But Spain had argued that both unemployment and immigration record be given more weight in the calculation.
Ahead of the proposals, Spain's foreign minister José Manuel Garcia-Margallo had asked that the fixed quota would reflect Spain's high unemployment rate (which stands at 24 percent) as well as the nation's previous efforts to absorb asylum seekers.
"Pledging to take in migrants to whom you cannot provide work would be, in my opinion, providing a bad service," he argued at a meeting in Brussels earlier this month.
The plan took no account of the "huge effort we are making to control migration from Morocco, Mauritania and Senegal which impacts the whole EU", Margallo added.
The new measure is intended to apply to the 24,000 Syrians and Eritreans who arrived in Italy after April 15th and are deemed to be in need of protection. A further 16,000 migrants who arrived in Greece from the two countries should also be relocated, the EU said.
The European Commission said the chosen number represents approximately 40 percent of asylum seekers in clear need of protection who arrived in Italy and Greece last year.
More than 1,800 migrants have died in the Mediterranean in 2015 - a 20-fold increase on the same period in 2014.
Some 60,000 people have already tried to make the perilous crossing this year, the UN estimates.
The European Agenda on Migration also includes proposals to beef up European border controls, including a military action plan to stop people smugglers and improving ways for qualified immigrant workers to get jobs.
The idea is backed by countries including Sweden, Germany, Austria and Italy, but faces strong opposition from, among others, Hungary and the UK.
The latter has already indicated it would use its legal right to opt out of the scheme so it has not been designated a quota.
Countries which agree to take in the Syrians and Eritreans will be offered €6,000 per person, with the greatest number to be moved to Germany.