The assault, which began yesterday, has seen Al-Nusra Front and allied groups seize three checkpoints around the large town of Jisr al-Shughur, the Syrian Observatory for Human Rights said.
The town is strategically located near the border with Turkey and along a key route leading west to the regime's stronghold of Latakia province.
"There are very fierce clashes ongoing since the early morning, and intense aerial bombing. The regime has conducted 34 air strikes in the area since Friday morning," Observatory head Rami Abdel Rahman told AFP.
Since the fighting erupted yesterday, 30 regime troops and 43 rebels -- including 13 Chechen fighters -- have been killed, Abdel Rahman said.
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The Islamist coalition was battling pro-government forces for three other checkpoints around the town, Abdel Rahman added.
On its official Twitter and Facebook accounts, Al-Nusra Front posted pictures of explosives and destroyed buildings, saying it would "purify Jisr al-Shughur" of President Bashar al-Assad's forces.
The local branch of the Syrian Revolution General Commission activist group said rebels began attacking from the north, leaving regime forces "floundering".
The regime still controls areas to the east, including the town of Ariha, a military base in Al-Mastumah and an air base at Abu Duhur.
But seizing Jisr al-Shughur would cut regime access to a major highway linking Idlib to Latakia -- Assad's home province -- farther west.
If opposition groups overrun it, it would enable them to launch additional attacks on Latakia, said Charles Lister, visiting fellow at the Brookings Doha Centre think tank.
Al-Nusra Front and its allies already control much of Idlib province.
Elsewhere, the extremist Islamic State group shot down a regime aircraft near a key military airport in southern Syria, with pro-IS Twitter accounts saying the jihadists had captured the pilot.