In the letter to the influential business newspaper on Monday, Margallo cited United Nations Resolution 2429.
This "calls for for the United Kingdom as administering power to put an end to the colonial situation in Gibraltar, stating that the continuation of such a situation was contrary to the purposes and principles of the U.N. Charter."
He went on to take Britain to task for "noncompliance" with the resolution before offering his own interpretation of the Treaty of Utrecht, the 1713 deal which handed the colony to Britain in perpetuity.
In Margallo's opinion, it does not include the waters of the Bay of Gibraltar, over which Spain still claims sovereignty.
This has been disputed by Gibraltar's authorities who claim that the UN's Convention of the Sea clearly defines Gibraltar's territorial waters.
Gibraltar recently placed a number of blocks in the sea here to create an artificial reef, causing conflict with Spanish fisherman and triggering a diplomatic spat between Spain and Britain.
As well as the positioning of the concrete, which Margallo described as "a violation of the most basic rules of environmental conservation", the letter went on to list a number of grievances that Spain has with the administration of Gibraltar.
Margallo claimed that "diverse types of smuggling" take place there and that therefore "[border] controls are essential for our country in the exercise of its responsibilities to the EU."
He went on: "Also problematic is Gibraltar's tax regime, which is characterized by opacity, especially regarding corporate tax," before adding, "More examples of violations of international obligations could be mentioned, but these are expressive enough."
Despite these disagreements, Margallo wrote that, "Spain does have friends, and views the U.K. as one."
But he added: "In every friendship it is necessary to cultivate trust and to address any conflicts with honesty and transparency."
He called on British Prime Minister David Cameron to remove the concrete blocks from the Bay of Gibraltar and enter into bilateral, international dialogue over the status of the territory.
In a strongly-worded jab at the UK he wrote: "Unlike the British government, the Spanish government is at ease in the context of international organizations, has full confidence in them, and is always willing to comply with their mandates."
Tensions over Gibraltar have escalated in recent weeks and some critics have accused Spain of using the issue to divert attention from the political scandals engulfing its own ruling Popular Party.