Eyewitness video shows the white contrails of Israel's missile defense system cutting across the sky, then moving to intercept Palestinian rockets fired from the Gaza Strip on Monday.
Islamist militants fired a barrage of rockets toward Jerusalem and southern Israel in what the Palestinian Hamas group said was punishment for violent confrontations between Israeli police and Palestinian protesters.
The rockets triggered air raid warnings, sending Israeli schoolchildren into bomb shelters.
There were no immediate reports of casualties from the rocket fire in Israel.
Retaliation from Israel was swift.
In Gaza, the health ministry said at least 20 people, including nine children, were killed in Israeli air strikes on the Palestinian territory.
Some of the injured were brought to this hospital in northern Gaza, where a child cried out in pain and a woman who lost her husband screamed as she followed his body out of the hospital.
Israel's military said it carried out strikes against armed groups, rocket launchers and military posts in Gaza after militants there crossed what Israeli Prime Minister Benjamin Netanyahu called a "red line" by firing on the Jerusalem area for the first time since a 2014 war.
"The terrorist organizations crossed a red line on Jerusalem Day and attacked us, on the outskirts of Jerusalem. Israel will respond very forcefully."
U.S Secretary of State Antony Blinken on Monday urged all sides to take steps to reduce tensions.
"Needless to say we are very focused on the situation in Israel, West Bank, Gaza. Very deeply concerned about the rocket attacks that we are seeing now, that need to stop, need to stop immediately."
Tensions have been rising for weeks in Jerusalem.
Jewish groups are trying to evict Palestinian residents from a neighborhood in the eastern part of the city.
As Israel celebrated "Jerusalem Day" earlier on Monday with marches marking its capture of eastern sections of the holy city in the 1967 Arab-Israeli war, violence erupted at the Al Aqsa mosque, Islam's third most sacred site.
The Palestinian Red Crescent Society said more than 300 Palestinians were injured in clashes with police who fired rubber bullets, stun grenades and tear gas.