The victims, a couple in their 70s, were hit by shrapnel as they headed to a shelter. The attack caused widespread damage and disrupted rail services near Tel Aviv. Police said the impact appeared to involve a cluster munition.
Emergency teams found heavy damage to homes and cars, while smoke rose over the area as sirens sounded across central Israel.
The overnight barrage hit several sites, with at least eight impact points reported in the Tel Aviv district and nearby Bnei Brak, where one person was lightly injured.
Shrapnel also damaged platforms at Savidor Central station, forcing a nationwide suspension of rail services.
The strike is part of ongoing exchanges since late February, after Israel said it killed senior Iranian figures on 17 March. Authorities say 14 people have died in missile attacks on Israel since the conflict escalated.