Images released by the state-run Syrian Arab News Agency showed blood on the mosque's carpets, holes in the walls, shattered windows and fire damage.
The Imam Ali ibn Abi Talib Mosque is located in an area of the Wadi al-Dhahab neighbourhood dominated by the Alawite minority in Homs, Syria's third-largest city.
SANA, citing a security source, said that preliminary investigations indicate that explosive devices were planted inside the mosque.
Authorities were searching for the perpetrators of the attack.
A security cordon was placed around the mosque, Syria's Interior Ministry said in a statement.
Tensions have flared across several parts of Syria in recent weeks as long-running sectarian, ethnic and political fault lines continue to destabilise the country, even as large-scale fighting has subsided.
The country has experienced several waves of sectarian clashes since the fall of president Bashar Assad last year.
Assad, himself an Alawite, fled the country to Russia.
Members of his sect have been subjected to crackdowns.
In March, an ambush carried out by Assad's supporters against security forces triggered days of violence that left hundreds of people dead, most of them Alawites.
Local officials condemned Friday's attack, saying it came "within the context of repeated desperate attempts to undermine security and stability and sow chaos among the Syrian people".
"Syria reiterates its firm stance in combating terrorism in all its forms and manifestations," the Ministry of Foreign Affairs added in a statement.
"Remnants of the former regime, ISIS militants and collaborators have converged on a single goal: obstructing the path of the new state by undermining stability, threatening civil peace and eroding the shared coexistence and common destiny of Syrians throughout history," the Syrian information minister said in a post on X.
The governments of neighbouring countries including Saudi Arabia, Jordan and Lebanon also condemned the attack.
In a statement, Lebanese President Joseph Aoun reaffirmed "Lebanon's support for Syria in its fight against terrorism".
On Monday, clashes have erupted intermittently between Syrian government forces and Kurdish-led fighters, the Syrian Democratic Forces, in mixed neighbourhoods in the northern city of Aleppo, forcing temporary closures of schools and public institutions and prompting civilians to shelter indoors.
A late-evening ceasefire was then announced by both sides amid ongoing de-escalation efforts.
The attack is believed to be the first targeting of a mosque in Syria since the overthrow of Assad.
In June, a suicide bombing at a Greek Orthodox church in Damascus killed 25 people.
The interior ministry blamed the attack on the Islamic State group.
with DPA
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