Very little is known about the concubines of Murad IV, principally because he did not leave sons who survived his death to reach the throne but, privy purse registers record the presence of a single haseki, Ayşe Sultan until the very end of Murad's seventeen-year reign. It is possible that Murad had only a single concubine until the advent of the second, or that he had a number of concubines but singled out only one as haseki. A vakf (meaning charitable foundation) inscription dating from 1628 reveals the existence of a concubine of Murad named Sanavber Hatun, who likely was of haseki rank. If Ayșe was initially his only concubine, it is probably his lack of male issue that prompted him to take another, for his sons all died in infancy.

Murad IV was for a long time under the control of his relatives and during his early years as Sultan, his mother, Kösem Sultan, essentially ruled through him. The Empire fell into anarchy; the Safavid Empire invaded Iraq almost immediately, Northern Anatolia erupted in revolts, and in 1631 the Janissaries stormed the palace and killed the Grand Vizier, among others. Murad IV feared suffering the fate of his elder brother, Osman II (1618–22), and decided to assert his power.

Murad IV put emphasis on architecture and in his period many monuments were erected. The Baghdad Kiosk, built in 1635, and the Revan Kiosk, built in 1638 in Yerevan, were both built in the local styles. Some of the others include the Kavak Sarayı pavilion; the Meydanı Mosque; the Bayram Pasha Dervish Lodge, Tomb, Fountain, and Primary School; and the Şerafettin Mosque in Konya.

During the siege of Baghdad in 1638, the city held out for forty days but was compelled to surrender.

Rumours had circulated that on his deathbed, Murad IV ordered the execution of his mentally disabled brother, Ibrahim (reigned 1640–48), which would have meant the end of the Ottoman line. However, the order was not carried out.

Murad IV's reign is most notable for the Ottoman–Safavid War (1623–39) against Persia (today Iran) in which Ottoman forces managed to conquer Azerbaijan, occupying Tabriz, Hamadan, and capturing Baghdad in 1638. The Treaty of Zuhab that followed the war generally reconfirmed the borders as agreed by the Peace of Amasya, with Eastern Armenia, Eastern Georgia, Azerbaijan, and Dagestan staying Persian, while Western Armenia, and Western Georgia stayed Ottoman. Mesopotamia was irrevocably lost for the Persians. The borders fixed as a result of the war, are more or less the same as the present border line between Turkey, Iraq and Iran.