Some critics of Israel argue that like apartheid South Africa, Israel is a colonial state whose laws and institutions enforce the subservient status of the indigenous population. Apartheid South Africa, however, was a uniquely repressive system through which South Africa's white minority enforced its domination over the black and other non-white racial groups through a host of separation laws. No such laws exist in Israel, which pledged itself to safeguard the equal rights of all citizens in its Declaration of Independence. Arab citizens of Israel have the full range of civil and political rights, including the right to organize politically, the right to vote and the right to speak and publish freely. Moreover, Israel has declared its acceptance, in principle, of a sovereign Palestinian state in most of the West Bank and Gaza Strip, to be established as the result of bilateral Israeli-Palestinian negotiations.

The international campaign to compare Israel to apartheid South Africa received global attention during the World Conference Against Racism, held in Durban, South Africa in 2001, which featured accusations that Zionism is racism and that Israeli policy is akin to South African apartheid. The apartheid analogy gained momentum in response to Israel's construction of the security fence, which began in 2003-2004, and stricter regulations at Israeli checkpoints and border crossings.

Some anti-Israel groups have made the apartheid analogy a fundamental aspect of their claims against Israel. The US Campaign to End the Israeli Occupation, a coalition with over 200 member groups around the country officially adopted an "anti-apartheid" framework at its annual conference in 2006 and since then, the group has arranged panel discussions, workshops, speaking tours and conferences focused on this issue. In November 2008, the US Campaign organized a nationwide two-week-long "Anti-Apartheid" speaking tour featuring Eddie Makue, a South African anti-apartheid activist, and former PLO lawyer Diana Buttu.

Similarly, Friends of Sabeel in North America (FOSNA), the North American offshoot of a Jerusalem-based anti-Israel organization, held a conference in October 2007 in Boston that promoted the apartheid analogy. The conference featured a keynote address by Archbishop Desmond Tutu, a world-renowned figure in the fight against apartheid in South Africa. Tutu not only likened Palestinian oppression to South African Apartheid, he also charged that the separation fence is an "illegal wall that has encroached on Palestinian land," and that Israel employs practices that "even apartheid South Africa had not…for example collective punishment."

In addition to the widespread use of the apartheid analogy within the anti-Israel movement, accusations that Israeli policy is comparable to apartheid has also found its way into the mainstream, most notably in Jimmy Carter's 2007 book Palestine: Peace Not Apartheid.