In Homs, at least 57 people, mainly civilians, were killed in a double car bombing, a monitoring group reported.
At least four blasts later struck the southern Damascus suburb of Sayyida Zeinab, causing at least 50 deaths, state media said.
So-called Islamic State has said it carried out the Damascus blasts.
Both Damascus and Homs have been targeted by Islamic State (IS) militants in the past.
Meanwhile, US Secretary of State John Kerry has said a “provisional agreement” has been reached with Russia on a partial truce in the conflict.
Both attacks targeted areas dominated by minorities within Islam reviled by the Sunni Muslim radicals of IS.
In Homs, the blasts happened in a predominantly Alawite district, the sect to which President Bashar al-Assad belongs.
In Damascus, at least four explosions were reported in Sayyida Zeinab, the location of Syria’s holiest Shia Muslim shrine, said to contain the grave of the Prophet Muhammad’s granddaughter.
State television reported at least 50 dead and 200 wounded. Other reports put the death toll higher.
Homs, one of the early centres of the uprising against President Assad, was once dubbed the “capital of the revolution”.
But rebels left the city late last year under a ceasefire deal, leaving the city in government hands.
The Amaq news agency, which is linked to the self-styled Islamic State, said IS militants had detonated a car bomb and then blown up explosive belts.
The district was hit by suicide attacks last month that left 71 people dead and which IS fighters also said they had carried out.
The Observatory also said that at least 50 Islamic State fighters had been killed in an advance by government troops, backed by Russian air strikes, east of the northern city of Aleppo in the past 24 hours.
Meanwhile, US Secretary of State John Kerry spoke optimistically about progress towards a possible ceasefire.
He had spoken to his Russian counterpart Sergei Lavrov, he said, and they had agreed on terms but details still needed to be worked out.
Earlier this month, world powers involved in Syria agreed to seek a “cessation of hostilities” but the Friday deadline has come and gone.
For his part, President Assad has said he hopes to be remembered as the man who “saved” Syria.
Asked by Spanish newspaper El Pais where he would see himself in 10 years’ time, he said: “If Syria is safe and sound, and I’m the one who saved his country – that’s my job now, that’s my duty.”
Mr Assad also said his army was close to encircling rebel-held parts of the key northern city of Aleppo, and were advancing on Raqqa, the main stronghold of IS fighters.
He said he was ready to implement a temporary truce as long as there were guarantees what he called “terrorists” would not use it to improve their positions.
Separately, Amnesty International has criticised Turkey for refusing entry to some Syrians wounded in the latest fighting, urging it to keep its border open.
Amnesty’s crisis response director, Tirana Hassan, said: “Turkey’s highly selective practice is appalling – only severely injured people are allowed entry to seek medical treatment while everyone else fleeing the violence is left unprotected.”