"I call for restraint to prevent the mood from becoming further inflamed so that, heaven forbid, we do not have additional tragedies," Netanyahu said in a statement early on Wednesday, adding that the death would be thoroughly investigated.
The incident killed yeshiva student Yosef Eisenthal.
Video from the protest obtained by The Associated Press showed a public bus dragging him for metres before running him over as onlookers jostled and screamed.
Police officers arrested and questioned the bus driver, who told investigators he was attacked by protesters before hitting the boy, Israel's police spokesperson said.
Protesters had been blocking the road and acting violently towards police officers, throwing eggs and other objects at them, the spokesperson said.
The violence reflected growing tensions between the Israeli authorities and the ultra-Orthodox, known as Haredim, as the government mulls plans to draft them into the military.
When Israel was founded in 1948, a small number of gifted ultra-Orthodox scholars were granted exemptions from the draft, which is compulsory for most Jews in the country.
But with a push from politically powerful religious parties, those numbers have swelled over the decades.
There is support for rolling back the ultra-Orthodox exemption among many secular Israelis, especially those who have served multiple rounds of duty in the latest war between Israel and the Palestinian militant Hamas group in Gaza.
Measures to draft the ultra-Orthodox have been met staunch opposition and occasional violence from religious protesters who claim serving in the military will destroy their way of life.
The pushback has created a political problem for Netanyahu, who relies on the support of religious parties in the Israeli parliament.
