The attacker, who was a resident of Occupied East al-Quds, entered a border guard post and wounded the two before being shot dead, according to the police.
One of the guards was seriously injured, the other sustained light injuries, police added, Al Jazeera reported.
Israel annexed Arab East al-Quds after the 1967 war.
A wave of violence that broke out in October 2015 has killed 255 Palestinians, 40 Israelis, two Americans, one Jordanian, one Eritrean and one Sudanese.
Others were killed during protests, in clashes or during air raids on Gaza.