The succession of al-Mundhir IV ibn al-Mundhir following the death of his brother Qabus in 573 was unpopular with the inhabitants of the capital, al-Hirah, because of his violent nature and his paganism.

A Persian governor, Suhrab, had been appointed and has ruled Hirah for a year, until Zayd ibn Hammad persuades the people to accept Mundhir as their king.

The events of the reign of Al-Mundhir IV are mostly obscure, except for the sack and razing of Hirah by the Ghassanids under al-Mundhir III ibn al-Harith in 575.

The Ghassanids, who successfully oppose the Persian-oriented Lakhmids of al-Hirah, prosper economically and engage in much religious and public building; they also patronize the arts and entertain the poet Nabighah adh-Dhubyani and, later, Hassan ibn Thabit at their courts.

Subsequent Roman distrust of Ghassanid religious unorthodoxy brings down al-Harith's successors, al-Mundhir and Nu'man.

(According to one story, which seems to be supported by Nabighah's later poetry, his enemies forged a satire against Nu'man, who was so enraged that Nabighah had to leave al-Hirah in great haste.)

Nabighah moves from Jabiyah to the enemy court of the Ghassanids in Syria, where he becomes a favorite, interceding several times on behalf of his tribesmen during their wars and defeats.

He never ceases to assert his innocence to Nu'man and eventually returns to al-Hirah.

Orthodox leaders of the Eastern Roman empire, viewing the Monophysite beliefs of the the Arab Ghassanids to be unacceptably heretical, reduce Ghassan to vassal status and dispatch imperial troops to secure its borders.

Two of the wives of Lakhmid king Al-Mundhir IV ibn al-Mundhir are known by name: the Jewish captive Salma bint al-Sa'igh, the mother of his heir Nu'man, and the Christian Mariya bint al-Harith ibn Djulhum.

Mundhir is known to have had twelve or thirteen sons.

He is succeeded in 580 by his son al-Nu'man III ibn al-Mundhir (r. 580–602), the last Lakhmid king of Hirah.