Seventy-three people were killed in the city of Jableh and another 48 died in Tartus further south, the Syrian Observatory for Human Rights monitoring group said.
Seven bombs -- most of them suicide attacks -- hit Jableh and Tartus almost simultaneously today morning.
Observatory head Rami Abdel Rahman said they were "without a doubt the deadliest attacks" on the two cities since Syria's conflict erupted in March 2011.
IS claimed the attacks via its Amaq news agency, saying jihadists had attacked "Alawite gatherings" in Tartus and Jableh.
Their populations are mostly Alawite.
IS is not known to have a presence in Syria's coastal provinces, where its jihadist rival and Al-Qaeda's local branch Al-Nusra Front is much more prominent.
But IS is notorious for using deadly sleeper cells to attack its enemies.
Syrian state media also reported the attacks but gave a total of 78 dead, 45 in Jableh and 33 in Tartus.
The attacks began at 9:00 am local time (0600 GMT) in Tartus, where steadfast regime ally Russia has long maintained a naval base.
The Tartus blasts were caused by one car bomb and two suicide bombers, the Observatory and police said.
A Facebook page sharing local news from Jableh, where another bus station was targeted, as was a government hospital, shared footage of people around fire trucks near several bombed-out cars.
A police officer in Jableh told AFP that one suicide attacker detonated his explosives inside the emergency room of the state-run hospital, while three car bombs caused the other blasts.
The Observatory said there were three suicide attackers and just one car bomb.
"The rising tensions and terrorist activity in Syria can only spark great worry," Kremlin spokesman Dmitri Peskov told journalists.
He said the attacks "demonstrate yet again how fragile the situation is in Syria and the need to take energetic measures to relaunch peace talks".
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