The militants opened fire on a military patrol on the Israeli side of the Israeli-controlled Golan Heights, a military spokesman was quoted by the Independent online.
Lt. Col. Peter Lerner said the patrol came under machine gun and mortar fire early on Sunday.
They returned fire towards Syria before an Israeli aircraft engaged the militants, striking a machine gun-armed car and killing its passengers.
All of the gunmen were suspected militants from "Shuhada al-Yarmouk," an IS offshoot which controls the area.
Lerner said none of the Israeli soldiers, from the Golani Brigade, were wounded in the clash.
Israel seized 1,200 sq. km (460 sq. miles) of the Golan from Syria in the Six-Day War of 1967 and later annexed it in a move never recognised by the international community.
Israel has been largely unaffected by the Syrian civil war next door.
While avoiding being drawn into the internal Syrian conflict, Israel attacks Syrian military targets when fire, even unintentional, spills over the demarcation line.
The Israeli army holds the Syrian government accountable for any fire from its territory, regardless of the source.