These include last month's bomb attack at the Hebrew University in Jerusalem, which killed nine people and injured more than 80.
Of the 15 Palestinian militants detained, five are from Arab East Jerusalem.
Israeli officials consider the arrests to be an important advance - the biggest Hamas cell that they have broken in East Jerusalem so far, says the BBC's James Reynolds in Jerusalem.
Israel is now warning of possible implications for the Palestinian population in East Jerusalem, our correspondent adds.
The 200,000 Palestinians who live in that part of the city have identity cards allowing them to travel freely throughout Israel - in contrast to Palestinians from the West Bank and Gaza who are for the most part not allowed into Israel.
'Paying the price'
Israel said it arrested the suspects over the weekend.
The cell was uncovered when some of its members were detained by an Israeli elite unit in Jerusalem - allegedly on their way to carry out another attack.
Cell's alleged attacks
March 9 suicide bombing at Moment Cafe, Jerusalem, kills 11 people
7 May suicide bombing at billiard hall at Rishon Letzion kills 15
Two bomb attacks on fuel tankers, one injured
Two bomb attacks on trailway track, injuring five
31 July bombing at Hebrew University kills nine
Security officials said the cell included a 29-year-old married Palestinian man who worked as a painter at the Hebrew University.
"Their methods of operation were very intelligent... Their next attacks would have only become more sophisticated," Israeli Deputy Public Security Minister Gideon Ezra told Israel radio.
Israel captured East Jerusalem in the 1967 Middle East war and annexed it in a move not recognised internationally.
Many residents refuse to acknowledge Israel's control of the city, which both sides see as their capital.
Israeli officials say they may have to pay what they call a dear social and eocnomic price as a result of being considered suspicious.