He was a highly influential figure in the Syrian politics from the beginning of the 1940s until his departure into exile in 1963, during this period he was able to introduce significant reforms towards more just and fairer society especially in relation to the agricultural sector and land redistribution against the feudal system.

His father Muhammad Rasheed Al-Hourani was a merchant who gradually bought agricultural lands and was fluent in Arabic and Turkish languages owning a large book collection, he died one year after the start of World War I (in 1915) due to an infection while distributing aid to the Armenian genocide survivors in Hama, Al-Hourani was only 4 years old when his father died.

Al-Hourani set about attacking this system and called for agrarian reforms, giving him considerable popular support in Hama and its province, and in 1943 he was elected as a deputy to the Syrian Parliament.

[6] However, as the dictator grew more autocratic his influence waned, and when al-Shishakli decided to ban the Arab Socialist Party in April 1952, he went into exile in Lebanon.

[8][better source needed] After the treaty of union between Syria and Egypt in 1958 Al-Hourani became vice-president of the United Arab Republic (UAR) under Gamal Abdel Nasser, a post he held until 1959.

After Nasser launched a bitter verbal attack on the Ba'ath Party in December that year, followed by a campaign of repression against its members, he resigned his position and went into exile in Lebanon.

When a 1961 military coup in Syria led to the dissolution of the UAR, Al-Hourani publicly supported it and signed a statement in favor of the secession (as did Bitar, but he later withdrew his signature).

[citation needed] In September 1962 he joined the "secessionist" (infisali) cabinet formed by Khalid al-Azm, drawing strong criticism from the Ba'athist and Nasserist movements.