The first seeds of Magen David Adom in Israel were planted at a meeting held in Philadelphia in October, 1918, attended by David Ben Gurion, Golda Meir and Henrietta Szold. There was great concern that the Jewish Legion of Palestine, otherwise known as the 38th Battalion of the Royal Fusiliers of the British Army during World War I, who were fighting to liberate Eretz Yisrael from Turkish rule, needed medical help. A Magen David Adom organization was organized to aid both the Jewish Legion and the settlers in Palestine. It was disbanded at the end of the war.
Magen David Adom (MDA) was officially chartered and recognized as an emergency lifesaving service as a result of the murderous riots of 1929, when Jewish farm and urban settlements were attacked by the Arab population, and were found to be lacking in even the most elementary first aid services. It was founded in Tel Aviv on June 7, 1930, by a group of seven Israeli doctors, as a one-room emergency medical service. MDA's first home was a dilapidated hut on the corner of Rothschild and Nahalat Benyamin streets in what was then the center of town.

A second MDA group formed in Haifa in 1931 and a third in Jerusalem in 1934. In 1935, a national organization was formed to provide medical services to the public and the Haganah. Its founding members were physicians, members of the Haganah and private citizens. At the time, the society's resources consisted of a small truck converted into an ambulance and several dozen dedicated volunteers.

In the years that followed, the society grew, especially in the wake of a second wave of anti-Jewish riots that broke out in April 1936 and lasted until the beginning of 1939. During that period, MDA gave first-aid training to the Haganah and the auxiliary police and medical aid to the wounded.

During World War II, MDA worked within the general framework of Israel's Civil Defense Organization, as an arm of the Jewish Legion of the British Forces. Photographs from that period show Magen David Adom volunteers in official uniforms. Magen David Adom became the medical service of the Haganah, and MDA members administered first aid alongside the Haganah fighters throughout the 1930s and 1940s. With the establishment of the State of Israel, some of the society's most important members and volunteers were among those setting up the medical corps of the Israel Defense Forces.

In July 1950, the Knesset (Israel's Parliament) ratified the Magen David Adom Law, which states that Magen David Adom will function as Israel's National Red Cross Society, acting in accordance with the Geneva conventions. Specifically, MDA was given responsibility for:

1. Providing auxiliary service to Israel's Army Medical Corps in wartime, including providing emergency medical care for the wounded and war refugees.
2. Providing civilian emergency transportation and medical and first-aid services and temporary shelter in emergency situations and disasters.
3. Organizing blood donations and maintaining sophisticated blood banks for civilian and military use.

Subsequently, MDA has played a major role in providing vital lifesaving services during each of Israel's wars, skirmishes and terrorist attacks, as well as in times of peace. The growing need and developing population of the new state brought about a parallel growth in MDA. New branches and first aid stations sprang up throughout the country. The first modern ambulances were purchased, and the society's blood, first aid and first aid instruction services were expanded.