The Rafah crossing, standing amidst rubble and ruins, is the sole route in or out for nearly all of Gaza's more than two million residents.
It was largely shut for most of the war, and reopening it to allow even limited access to the outside world is one of the last steps required under the initial phase of a US-brokered ceasefire reached in October.
The crossing reopened on Monday morning. Some 50 Palestinians had been expected to enter the enclave with a similar number leaving.
Many of those seeking to leave are hospital patients awaiting specialised medical care.
By nightfall, Israel had permitted 12 Palestinians to re-enter the enclave, Palestinian and Egyptian sources said.
A further 38 had not cleared security and would wait on the Egyptian side of the crossing overnight, they said.
Israel permitted five patients escorted by two relatives each to cross to the Egyptian side, the sources said.
That brought the total number entering and exiting to 27.
Palestinian officials blamed delays on Israeli security checks. Israel's military had no immediate comment.
Some 20,000 Gazans are hoping to leave Gaza for treatment abroad. Despite the slow reopening, many of them said the step brought relief.
"The crossing is a lifeline for Gaza, it is the lifeline for us, the patients," said Moustafa Abdel Hadi, 32, who receives kidney dialysis at Al-Aqsa Martyrs Hospital in central Gaza.
"We want to be treated in order to return to live our normal life."
Israel seized the border crossing in May 2024, about seven months into the Gaza war. Since then, it has largely been closed apart from a brief period during an earlier truce in early 2025.
Reopening the crossing was one of the requirements under the October ceasefire that outlined the first phase of US President Donald Trump's plan to stop fighting between Israel and Palestinian Hamas militants.
In January, Trump declared the start of the second phase where the sides would negotiate the shattered enclave's future governance and reconstruction.
Even as the crossing reopened, Israeli strikes killed at least four Palestinians on Monday, including a three-year-old boy, in separate incidents in the north and south of the Strip. The Israeli military had no immediate comment on the incidents.
In the war's early months before Israel shut the crossing, some 100,000 Palestinians left for Egypt through Rafah.
Though Egypt has repeatedly made clear it will not allow a large-scale exodus, the route is seen as vital for wounded and sick Palestinians to seek medical care.
While it was closed, only a few thousand were allowed out for medical treatment in third countries through Israel.
Palestinians seeking to cross at Rafah will require Israeli security approval, three Egyptian sources said. Reinforced concrete walls, topped with barbed wire, have been installed along the crossing area, the sources said.
Under the first phase of the ceasefire, major combat was halted, hostages held in Gaza were released in return for thousands of Palestinian prisoners held by Israel, and a surge in humanitarian aid was promised.
Israeli forces hold more than 53 per cent of Gaza's territory, where they have ordered residents out and razed many remaining buildings. Residents are now confined to a strip along the coast, most living either in makeshift tents or damaged buildings.
The next phase of Trump's plan foresees Hamas giving up its weapons and relinquishing control to an internationally backed administration that would oversee reconstruction, including luxury residential buildings along the Mediterranean coast.
