Muhammad and Khadija may have had six or eight children. (Sources disagree about number of children: Al-Tabari names eight; the earliest biography of Muhammad by Ibn Ishaq, names seven children; most sources only identify six).

Their first son was Qasim, who died after his third birthday (hence Muhammad's kunya Abu Qasim). Khadija then gave birth to their daughters Zaynab, Ruqayyah, Kulthum and Fatima; and lastly to their son Abd Allah. Abd Allah was known as at-Tayyib ('the Good') and at-Tahir ('the Pure'). Abd-Allah also died in childhood.

Two other children also lived in Khadija's household: Ali ibn Abi Talib, the son of Muhammad's uncle; and Zayd ibn Harithah, a boy from the Kalb tribe who had been kidnapped and sold into slavery. Zayd was a slave in Khadija's household for several years, until his father came to Mecca to take him home. Muhammad insisted that Zayd be given a choice about where he lived, and Zayd decided to remain where he was, after which Muhammad legally adopted Zayd as his own son.