The treaty was signed between the two countries' defense ministries on April 19, 1995.
Tbilisi's move comes after two Georgian reconnaissance planes were allegedly shot down over the unrecognized republic of Abkhazia's airspace on Sunday.
Irakli Torondzhadze, director of the Foreign Ministry Russia Department, handed Andrei Smag, Russia's envoy to Georgia, official notice.
A Georgian deputy defense minister said his country had seen no practical benefit from the treaty with Russia.
"Georgia has long stopped participating in any defense or military-technical cooperation programs within the CIS," Batu Kutelia said, adding he hoped the Russian side would treat the announcement "with understanding."
Russia's Embassy in Tbilisi confirmed that it had received formal notice from Georgia.
Embassy press attache Alexander Savinov said the note "has been transferred to Moscow via official channels," but that "no instructions have been received from Moscow yet."
Asked whether the note had set out the reasons for Georgia's decision to withdraw from the agreement, he said: "At this stage we are not in a position to comment."
The CIS unified air defense system includes Armenia, Belarus, Kazakhstan, Kyrgyzstan, Russia, Tajikistan, Turkmenistan, Uzbekistan and Ukraine.
Georgia previously withdrew from the CIS Defense Ministers Council although it formally remained in the CIS unified air defense system.
Abkhazia said earlier on Monday its air defense forces had detected another Georgian reconnaissance plane, but decided not to engage it.
"Although we downed two drones yesterday, today our [Abkhaz] radars picked up another surveillance drone... which flew from the direction of Georgia," Defense Minister Merab Kishmariya told RIA Novosti adding that the unmanned aerial vehicle remained over Abkhazian territory for 10 minutes, but the decision was made not to shoot it down.
Russia's foreign minister said Moscow is extremely concerned over Georgia's course to resolve its conflicts with breakaway republics by military force.
"This course unfortunately undermines all agreements, primarily those regarding the settlement of the Georgian-South Ossetian and Georgian-Abkhaz conflicts," he said.
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Any anti-ISIL operation in Iraq cannot be effective unless the Islamic State is attacked in Syria. But the final statement of the Paris Conference did not mention Syria as a precaution against disunity in the coalition and with due regard for the Russian position. Professor of the Chair of Modern East Department of History, Political Science and Law in RSUH