TEL AVIV—Israel pounded the Gaza Strip with artillery shells and about 20 airstrikes on Wednesday, killing Hamas's top military commander and at least seven other people in the most violent assault on the coastal territory in four years.

The Israeli strikes came in retaliation to a wave of missile attacks on Israeli territory in recent days from the Gaza Strip. Palestinian militants responded Wednesday by firing dozens of rockets at nearby Israeli communities. Hamas leaders called the attack an act of war and Hamas's armed wing warned on its website that Israel had "opened the gates of hell," raising fears that the fighting could escalate into full-blown war.

The Gaza assault thrusts the Israeli-Palestinian conflict back into the region's spotlight for the first time since Arab Spring uprisings swept the region nearly two years ago. Since the last Israeli-Hamas war ended in 2009, several of the Middle East's core relationships have fundamentally changed. An Islamist government has come to power in Egypt, on Israel's southern border. To the east, Syria is embroiled in war.

The resurgent violence in Israel stands as an early test of how those historic changes will impact and reshape a conflict that has in many ways defined the region's politics for much of the past century. Among the lingering questions are whether democratically elected Islamic leaning governments will chart a different course than their predecessors in dealing with the Israeli-Palestinian conflict. Another is how Hamas's break with Syria's regime, long its chief regional patron, will impact its policies.