The Syrian Observatory for Human Rights, a Britain-based monitor of the war, said IS was no longer present anywhere in the province for the first time in three years.
The army, backed by ally Russia, launched a campaign against IS in Hama in early September, capturing some 50 villages and the strategic town of Uqayribat, the Observatory said.
"Today, regime forces managed to take control of all the last remaining villages in the hands of Daesh (IS) in eastern Hama province after more than a month of fierce clashes between the two sides," Observatory director Rami Abdel Rahman said.
There was no immediate announcement in Syrian state media, but the Al-Watan newspaper, which is close to the government, reported that "the army has taken complete control of eastern Hama province."
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"Daesh is no longer present in Hama province," it added.
The government holds large parts of Hama province, and all of the provincial capital.
But jihadists and other rebels hold pockets of territory in the northeast and south.
IS's loss of Hama province comes after they were forced in June to withdraw from their last positions in Aleppo province further north.
The US-backed Syrian Democratic Forces, an alliance of Kurdish and Arab fighters, is battling to oust IS from their onetime stronghold of Raqa.
The SDF is also fighting IS in neighbouring Deir Ezzor province, where the regime is waging its own campaign against the jihadist group as well.
More than 330,000 people have been killed in Syria since the conflict began with anti-government protests in March 2011.