The document was signed at a meeting of the Union State Supreme Council, co-chaired in Moscow by Russian President Dmitry Medvedev and his Belarusian counterpart Alexander Lukashenko.
Military cooperation between the two former Soviet republics has gained momentum recently, bolstered in part by recent U.S. moves to deploy missile defense elements in Poland and the Czech Republic.
The Kremlin said the document "is a serious step in the development of military and military-technical ties between Russia and Belarus" and "it will significantly boost the defense capabilities of both countries."
Col. Gen. Alexander Zelin, commander of the Russian Air Force, previously said the integrated air-defense system would comprise five Air Force units, 10 anti-aircraft units, five technical service and support units and one electronic warfare (EW) unit.
The system will be placed under the command of a Russian or Belarusian Air Force or Air Defense Force senior commander, at the presidents' discretion.
Belarus has several Russian-made S-300 air defense battalions on combat duty and is negotiating the purchase of advanced S-400 systems from Russia, which will be made available by 2010.
Russia's defense minister said last year Moscow would continue to supply arms and military hardware to Belarus at subsidized rates and on a priority basis.