In line with the lack of diplomatic relations and continuous state of war, there have been virtually no economic or cultural ties between Israel and Syria, and a limited movement of people across the border.

This led to a period of escalated fighting as the Israelis sought to prevent this diversion project which threatened to severely damage their ability to provide fresh-water to their population and agriculture (attempts to negotiate a solution by UN mediators failed).

In fact, escalation of incidents between Israel and Syria in late 1966 and spring 1967 was one of the prime causes leading to the crisis that precipitated the Six Day War.

Prior to the 1967 Six-Day War, intermittent hostilities centered on the demilitarized zones, water issues and shelling and infiltration from the Golan Heights.

The first high-level public talks aimed at a permanent resolution of the conflict between Israel and Syria were held at and after the multilateral Madrid Conference of 1991.

However, the parties were unable to come to an agreement due to President Bill Clinton's failure to consult with the Syrian President, Hafez al-Assad during the negotiating process, Israeli Prime Minister Ehud Barak's backtracking on the issue of the northeastern shore of the Sea of Galilee and Syria's nonnegotiable demand that Israel withdraw to the positions it held on 4 June 1967 (which meant Israel would relinquish its claim to territory occupied by the Syrians in the early 1950s in contravention to the 1949 Armistice Agreement—including the north-eastern shore of the Sea of Galilee).

The peace negotiations collapsed following the outbreak of the second Palestinian (Intifada) uprising in September 2000, though Syria continues to call for a comprehensive settlement based on UN Security Council Resolutions 242 and 338, and the land-for-peace formula adopted at the 1991 Madrid conference.

The September 2007 Operation Outside the Box attack by the Israeli Air Force destroyed a facility that Israel claimed was a nuclear site in the Deir ez-Zor region.

Israeli Foreign Minister Avigdor Lieberman responded by saying that the Syrian military would be defeated in a war with Israel, and Assad and his family would be forced from power.

[12] On 11 July 2018, Netanyahu stated that Israel was not seeking to take action against Assad, but urged Russia to facilitate the withdrawal of Iranian troops from Syria.

[13] On 2 August 2018, Lieberman stated his belief that Syrian troops regaining control of the country's border with Israel would reduce the chance of conflict in the Golan Heights by providing "a real address, someone responsible, and central rule".

[15] In January 2021, Syria denied reports of a Russia-mediated meeting at the Khmeimim Air Base between former IDF Chief of Staff Gadi Eisenkot and Syrian National Security Bureau head Ali Mamlouk.

[21] On May 20, 2022, an Israeli "aggression" launched from the Golan Heights and targeting southern sections of Damascus killed three individuals and inflicted minor material damage, according to the Syrian Ministry of Defense.

[22] In October 2023, the Tahrir al-Sham's clerics held prayers for a Palestinian victory in the Israel–Hamas war and said it celebrated Hamas' jihad while condemning its ties with Shiite-led Iran.

[24] On 1 April 2024, Israel's air strike on an Iranian consulate building in the Syrian capital Damascus killed an important senior commander of the Islamic Revolutionary Guards Corps (IRGC), Brig Gen Mohammad Reza Zahedi.

[25] During the decisive battle of Damascus and subsequent fall of the Assad regime on 7–8 December 2024, Israeli forces initiated temporary military operations in Syria's Quneitra Governorate.

[26] A Turkish news report claimed that Assad provided Israel with a map of Syria's military sites before fleeing to Russia.

[32] The aid consisted of medical care, water, electricity, education or food and was given to Syrians near the ceasefire line between Israel and Syria, often escorted across by Israeli soldiers.

[37] Shortly after of the 2023 Turkey and Syria earthquake, the State of Israel received a Government of Turkey request for assistance from the Israel Defense Force in search and rescue and recovery efforts, and the IDF deployed a large team of approximately 500 search and rescue professionals to assist the Turks in the aftermath of the earthquake.