His assignment gave him command over the nomadic Arab tribes of Syria and obliged him to provide auxiliary troops in times of war and guard the desert frontier from the Mongol Ilkhanate in Iraq.
In 1279/80, Isa defected from Baybars' successor, Qalawun, and joined the rebellion of the Mamluk viceroy of Syria, Sunqur al-Ashqar.
Isa was reinstalled by 1280, and in the following year, played a decisive role as a commander in the Mamluk victory over the Ilkhanate at the Second Battle of Homs.
[2] By the early 13th century, the Al Fadl dominated the desert region between Homs in the west to the Euphrates valley in the east and from Qal'at Ja'bar southward through central Najd.
[11] The next year, Isa was present in Cairo to bear witness that al-Mustansir's successor and kinsman, al-Hakim, was indeed a member of the Abbasid line.
[13] Their conflict dissipated as the Mamluks gave the Al Mira virtual independence in the southern desert, while maintaining Isa as amir al-ʿarab.
[12] In early 1265, Isa was dispatched by Baybars to lead a raid against Ilkhanid-held Harran as a diversion for a Mamluk expedition aimed at relieving their Anatolian fortress of al-Birah from an Ilkhanid siege; al-Birah's defenders withstood the siege and the Ilkhanids retreated in haste with the arrival of Mamluk forces in February.
[16] News of this turn of events prompted Baybars to secretly rush to Syria from Egypt on 15 September 1270 and secure Isa's commitment to the Mamluks.
[16] Afterward, Baybars honored him and agreed to free the hostages, restore Isa's grant, and distribute to the Bedouin tribes large amounts of wheat.
[14] In 1273, Isa led raids against Ilkhanid-held Anbar in western Iraq on orders from Baybars, possibly to divert Ilkhanid forces from an expedition against Syria.
[14][19] The Ilkhanids and their Armenian and Georgian allies took advantage of the intra-Mamluk strife and an invitation by Sunqur to invade Syria, and sacked Aleppo.
[18] Isa reprimanded Sunqur for inciting the Muslims' enemies to attack and urged him not to betray Islam in his late age.
He was succeeded by his son Muhanna ibn Isa, who inherited his emirate,[26] and became the lord of the ancient oasis town of Palmyra.
[14] For the next quarter century, Muhanna and another of Isa's sons, Fadl, held the office of amir al-ʿarab with minor interruptions.