The first to accept Islam were Khadijah, his close friend Abu Bakr, the young ʿAli and his freed servant Zayd ibn Harithah. Through Abu Bakr, others such as ʿUthman ibn ʿAffan embraced Islam. For about three years the call was shared quietly.

Then Allah commanded: "And warn your nearest kindred" (26:214). He called Quraysh from Mount Safa and proclaimed the message openly. Opposition grew, led by men such as Abu Jahl and Abu Lahab. The weak and enslaved suffered most: Bilal ibn Rabah was tortured in the scorching sun yet kept repeating "One, One"; Yasir and Sumayyah were killed for their faith, Sumayyah becoming the first martyr of Islam.

In the fifth year of prophethood, a group of Muslims migrated to Abyssinia, where the Christian king al-Najashi (the Negus) gave them protection after hearing Jaʿfar ibn Abi Talib recite from Surah Maryam. In Makkah, the conversion of Hamzah and then ʿUmar strengthened the Muslims.

Quraysh then imposed a boycott on Banu Hashim, who were confined for about three years in the valley known as Shiʿb Abi Talib, suffering severe hunger. Soon after it ended, in the tenth year, Khadijah and Abu Talib both died — the Year of Sorrow.

Seeking support, the Prophet ﷺ went to Taʾif, but its leaders rejected him and had him driven out with stones. When the angel of the mountains offered to crush the town, he refused, hoping that their descendants would worship Allah alone. Around this time Allah honoured him with al-Isra and al-Miʿraj — the night journey to Jerusalem and the ascension through the heavens (17:1), when the five daily prayers were made obligatory.