"A Eurofighter crashed on landing at the start of the runway of the Moron base," near Sevilla, a ministry spokeswoman told AFP.
The sole pilot of the plane, an air force captain, was killed, a defence ministry spokesman said.
The Moron air base is shared by Spain and the US Air Force, but only Spain operates the Eurofighter jet.
The Eurofighter, a multi-purpose twin-engine fighter jet introduced in 2003, is built by a consortium made up of British defence group BAE, European aerospace group Airbus and Italian defence contractor Finmeccanica.
The Eurofighter consortium, Europe's largest defence programme, is in fierce competition with other fighter-jet makers such as Lockheed Martin, Boeing and Dassault Aviation.
Last month the head of Airbus' defence division, Bernhard Gerwert, said the consortium would stop making the Eurofighter jet in 2018 if it did not win new export contracts for the fighter jet.
Talks were underway to sell Eurofighter jets outside of Europe, to Qatar, Saudi Arabia, Kuwait and Malaysia, he said.
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