The experts said the annexation would be a "serious violation" of the United Nations charter and the Geneva Conventions, and would only intensify human rights violations in the West Bank.
Israeli Prime Minister Benjamin Netanyahu aims to begin a process of annexing West Bank settlements and the Jordan Valley from July 1, as part of a US peace initiative.
The experts said the 53-year Israeli occupation of the West Bank had been the source of "profound human rights violations" against the Palestinians, chiefly the denial of the right of self-determination among a long list of other alleged violations.
"These human rights violations would only intensify after annexation," the experts said.
"What would be left of the West Bank would be a Palestinian Bantustan, islands of disconnected land completely surrounded by Israel and with no territorial connection to the outside world.
"Israel has recently promised that it will maintain permanent security control between the Mediterranean and the Jordan River.
"Thus, the morning after annexation would be the crystallisation of an already unjust reality: Two peoples living in the same space, ruled by the same state, but with profoundly unequal rights. This is a vision of a 21st-century apartheid."
The more than 40 independent special rapporteurs along with a range of UN working groups on various rights issues who signed the statement do not speak for the UN but report their findings to it.
The experts said that Israel’s annexation of East Jerusalem in 1980 and the Syrian Golan Heights in 1981 saw condemnation but no meaningful response from the international community.
"This time must be different,” they said.
"The lessons from the past are clear: Criticism without consequences will neither forestall annexation nor end the occupation.”
The experts voiced "great regret” about Washington’s role in "supporting and encouraging Israel’s unlawful plans”, saying the United States should be "ardently opposing” an imminent breach of international law "rather than actively abetting its violation”.