The Islamist uprising in Syria comprised a series of protests, assassinations, bombings, and armed revolts led by Sunni Islamists, mainly members of the Fighting Vanguard and, after 1979, the Muslim Brotherhood, from 1976 until 1982. The uprising aimed to establish an Islamic republic in Syria by overthrowing the neo-Ba'athist government, in what was described by the Ba'ath Party as a "long campaign of terror".

After 1980, the popular resistance to Ba'athist rule expanded, with a coalition of Islamist opposition groups coordinating nation-wide strikes, protests and revolts throughout Syria. During the violent events, resistance militias attacked Syrian Arab Army bases and carried out political assassinations of Ba'ath party cadres, army officials, Soviet military advisors, and bureaucrats linked to Assad family. Civilians were also killed in retaliatory strikes conducted by security forces. The uprising reached its climax in the 1982 Hama massacre, during which the Syrian government killed between 5,000-40,000 civilians.

In context, the insurgency traces its origins to multiple factors. Historical ideological friction is a result of the Ba'ath Party's ultra-secularist foundation versus the Muslim Brotherhood's religious foundation. Muslim Brotherhood believed that Islamic religion had the central role in directing the laws of the state. On the other hand, secular Ba'athist ideology emphasized Arab nationalism and advocated the replacement of religion with socialism.

This friction became heated following the 1963 Ba'ath Party coup which saw the Party claiming sole power in the country and subsequently outlawing all other organised opposition. In response, the Muslim Brotherhood encouraged general protests across the country. These protests were most acute in the city of Hama, long considered "a stronghold of landed conservatism". During the 1964 Hama uprising, Ba'ath Party responded violently, crushing the revolt with brutal force.

Muslim Brotherhood was forced to continue its activities clandestinely. In the party, the ideological dispute began widening towards a sectarian one; as dominance of Alawite elites in the Ba'athist military, bureaucracy and politics became visible after the Old Guard was overthrown by the neo-Ba'athist military wing of Alawite General Salah Jadid in the 1966 coup. The Syrian Muslim Brotherhood fractured over disputes of the best course of action. Much of the party leadership was afraid to directly oppose the Syrian government, fearing that a violent confrontation could cause more harm than good. In contrast, several of the most radical members of the party split off to form the "Fighting Vanguard", led by Marwan Hadid. The Fighting Vanguard was willing to challenge the government by conducting assassinations and sabotage actions.

On 13 November 1970, Hafez Al Assad launched a coup which saw him gain sole power. To cement his power, on 31 January 1973, Assad implemented a new constitution which led to a national crisis. Unlike previous constitutions, this one did not require that the president of Syria must be a Muslim, leading to fierce demonstrations in Hama, Homs and Aleppo organized by the Muslim Brotherhood and the ulama. They labelled Assad as the "enemy of Allah" and called for a jihad against his rule. Under pressure, Assad returned the requirement and convinced Lebanese cleric Musa al-Sadr to issue a fatwa proclaiming the Alawite minority to be part of Shia Islam. The 1973 constitution greatly increased the support for Hadid's Fighting Vanguard, and many Muslim Brotherhood members defected to his faction or at least began to support it. He subsequently reorganized his group to increase the number of attacks, hoping to provoke the Syrian government into a crackdown that would force the Muslim Brotherhood into open rebellion.

Robert D. Kaplan has compared Assad's coming to power to

"an untouchable becoming maharajah in India or a Jew becoming tsar in Russia—an unprecedented development shocking to the Sunni majority population which had monopolized power for so many centuries."