The Syrian Observatory for Human Rights also reported that around 170 jihadists were killed in US-led air strikes in the past 48 hours in support of Kurdish forces in northeast Syria.
The loss of Al-Mastumah base leaves only a few positions in regime hands in Idlib, a region that borders Turkey and neighbours the government stronghold of Latakia province on the Mediterranean coast.
"All regime forces have withdrawn from Al-Mastumah, the largest regime base in Idlib, leaving it completely in the hands of opposition fighters," said Rami Abdel Rahman, head of the Observatory.
Al-Qaeda affiliate Al-Nusra Front, a key player in the Army of Conquest grouping that has seized much of Idlib in recent weeks, announced Al-Mastumah's capture online.
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"With the help of God, Al-Mastumah was completely liberated after Al-Nusra Front stormed it from the south," Al-Nusra said on Twitter.
Abdel Rahman said regime troops withdrawing from the base were leaving towards Ariha, now one of the last government bastions in Idlib.
State television said the army was "taking defensive positions" outside of Ariha, implying that army units had withdrawn from Al-Mastumah itself.
The Army of Conquest had since edged closer to Al-Mastumah, where regime forces fled after withdrawing from Idlib city.
There was no immediate toll in the capture of the military base.
In Hasakeh province of northeast Syria, around 170 jihadists were killed in 48 hours, mostly in "very intense air strikes" by the US-led coalition, the Observatory said.
The US military said the alliance's warplanes carried out seven strikes near Hasakeh.
Elsewhere today, IS attacked a village in the Druze heartland of southern Syria, killing six people before pro-regime gunmen expelled them.