The crossing at Rafah will remain open in both directions until Monday for medical and humanitarian reasons, students and the return of Palestinians stranded outside, Al Jazeera reported.
Iyad al Buzom, Gaza's interior ministry spokesperson, said the opening is "the start of a new phase of the Rafah crossing" and added that plans for a permanent crossing will "end the suffering of people in Gaza."
Rafah is the main exit for the 2 million Palestinians along the Gaza Strip.
Israel established a blockade on the area by land, air and sea after Hamas ousted the Palestinian Authority from Gaza in 2007 and took over the territory's crossings.
Since Egyptian President Abdel Fattah el-Sisi's rise to power in 2014, the nation has usually kept its crossing closed. The last time Egypt opened the crossing was in late August.
On Nov. 1, Hamas handed over Gaza's crossing with Egypt and Israel to the Palestinian Authority.
The disputing Islamic groups Hamas and Fatah reached a deal in mid-October to restore the Palestinian Authority's governing control over the Gaza Strip. Fatah controls the West Bank.
Hosam Salem, a Palestinian journalist at the crossing, told Al Jazeera about 10 buses had left the Strip by 7 p.m. and one bus had entered. He estimated that about 500 Palestinians had been allowed to leave.
At its crossing, Israel allows goods and people to pass in both directions daily with restrictions.
"We need the Rafah crossing to open and allow for the transport of people and goods," Maher Taba'a, the spokesman of the Gazan Chamber of Commerce, said Wednesday to The Jerusalem Post. "I believe opening it on a permanent basis will have an enormous impact on Gaza's economy."