阿米娜在穆罕默德六歲的時候逝世，轉由祖父阿布德照顧，他在作為哈希姆氏族領導人的祖父身邊看到了他的為人舉止和如何解決族人之間的爭端[41]。隨著阿布德的逝世，穆罕默德的伯伯阿布·塔利卜承擔起照顧他的責任[42]。阿布·塔利卜把穆罕默德視同己出，穆罕默德也把伯母法蒂瑪·賓特·阿薩德（阿拉伯语：فاطمة بنت أسد）稱作母親，並指她甚至會優先給他餵食和穿衣，然後才到她自己的親生子女[43][44]。
包括阿卜杜拉·伊本·朱丹（意大利语：'Abd Allah ibn Jud'an）在內的古萊什部落的氏族領導人在他的家中會晤，約定他們將會支持受害人伸張正義[57]。由於古萊什部落亦意識到一些頂尖商人與普羅大眾之間的鴻溝會破壞社會穩定，加劇部落之間的敵對，美德同盟亦承諾富人須把一部分的利潤分給窮苦大眾[62]。美德同盟對實現阿拉伯的和平起了重要的作用，據說在美德同盟締結後，阿拉伯長時間都沒有爆發戰事。穆罕默德也參與了美德同盟的締結，可能是他日後在麥地那解決爭端時用作參考的案例。[63]
當穆罕默德到25歲的時候，塔利卜把他介紹給商人赫蒂徹，讓她僱用穆罕默德帶領商隊前往大馬士革[65]。赫蒂徹經歷過兩段婚姻，但都成為了寡婦，她繼承了兩位丈夫的遺產，因此得以擴充她的商隊[66]。史學家伊本·賽德（阿拉伯语：محمد بن سعد البغدادي）及塔巴里描述了兩人協商的細節，稱赫蒂徹向穆罕默德提供了有利於他的條款。這次的商業合作取得了成功，穆罕默德得以用一倍的價格出售了赫蒂徹的商品[67]。
在受啟成為先知之前，穆罕默德在經商期間接觸過基督徒和猶太人，因此對他們的宗教信仰有基本的認知[85]。穆罕默德對他們之間的爭論感到困惑，猶太人稱上帝是他們的至高神，但基督徒卻稱那已經成為歷史，並指上帝通過一位叫基督的凡人具現化，然而穆罕默德直覺上認為創造宇宙萬物的上帝不會是一介凡人，並且他不會不公平地厚待了某一個人[86]。據指穆罕默德曾經遇到自稱信奉亞伯拉罕宗教的宰德·伊本·阿姆魯（阿拉伯语：زيد بن عمرو بن نفيل），他拒絕了穆罕默德奉獻給偶像的祭品，並責備他崇拜偶像和食用異教神祇的祭品，穆罕默德深受他的影響[87]。
這時的麥地那有許多明爭暗鬥，包括兩個主要的阿拉伯部落之間、追隨穆罕默德遷徒的遷士與麥地那的穆斯林輔士之間及猶太人與穆斯林之間[165]。穆罕默德很快便與這裡的各個部落和他率領的穆斯林達成協議，稱為《麥地那憲章（阿拉伯语：صحيفة المدينة）》。根據協議，麥地那所有信奉各個宗教的社群都會團結起來互相支持，特別是在受到攻擊的時候，又訂明了穆罕默德在各方發生爭議的時候擔當仲裁者。[166][167]學者安東尼·布萊克（德语：Anthony John Black）認為，根據《麥地那憲章》，穆罕默德是要在部落聯盟的架構以外按照他的使命打造新民族[168]。
為了支持麥地那新建的穆斯林社群，穆罕默德與穆斯林搶略往來麥加的商旅[171]。穆罕默德可能是為了解決穆斯林社群的經濟問題而訴諸搶略，瓦特解釋「搶略是阿拉伯漠民的常態」[172][173]。在他抵達麥地那僅僅八個月後的623年2月，穆罕默德下達了劫掠古萊什部族商隊的命令，他本人在隨後亦親自參與了這些行動，其中的納赫拉伏擊戰（阿拉伯语：سرية عبد الله بن جحش）最為重要[174][175]。他們在阿拉伯人視為聖月的時間發動了這次襲擊，攻擊和殺害了沒有防備的麥加人[176]。
在麥地那，穆罕默德所獲的《古蘭經》啟示交代了巴德爾戰役的戰利品分配問題，亦談及如何處理犠牲戰士遺下的孤兒和寡婦，聖訓亦提到他試圖在麥地那建立社會秩序[192]。歷史學家理查德·A·加布里埃爾（英语：Richard A. Gabriel）形容穆罕默德最大的成就之一是建立了穆斯林社會制度，大大改變了阿拉伯的社會秩序[193]。
埃及作家穆罕默德·侯賽因·海卡爾（阿拉伯语：محمد حسين هيكل）在他的著作裡詳細描述穆罕默德在二十多歲時的面貌，稱他有一張俊朗的面孔，身材中等，大大的腦袋有一頭濃密的黑髮。他的額頭寛闊，大大的黑眼睛配上濃密的眉毛，眼側微紅，睫毛長長；鼻子美觀，牙齒整齊，鬍子厚密，頸部修長，胸肩闊大。他的膚色淺白，手腳厚實。[260]穆罕默德的朋友形容他體格魁梧，皮膚「像女人一樣」紅潤，偌大的深色眼睛動人心魄[261]。標榜是由穆斯林澤利姆（Zelim）寫給一位猶太拉比的《猶太人的偉大解放者穆罕默德與摩西的相似之處》（Parallele entre Mahomet et Moise le grand liberateur des Juifs）裡亦有類似描述，形容他五官生動、神態高貴，澤利姆強調這樣的描述是由穆罕默德的敵人所載，不能被視為奉承之語[262]。
聖行補足了《古蘭經》，有時可以解釋經文的內容，或提供更多細節，穆斯林應當仿效穆罕默德的這些聖行[330]。伊斯蘭教學者馬哈茂德·阿尤布（阿拉伯语：محمود محمد أيوب）稱「聖行在本質上不是宗教聖典，而是穆斯林在他們的生活當中的榜樣」[331]。穆斯林文化和一些行為習慣都是參照了穆罕默德的做法，例如穿鞋、梳頭等動作都是先右後左[332]。證信、禮拜的宗教課業都是源自聖行，而齋戒、朝覲的細節規定也是通過聖行而訂立[333]。
學者德尼·格里伊（維基數據：Q113828747）表示，早於穆罕默德的先知有奇跡相助，確認和肯定他們所傳達的訊息，然而《古蘭經》裡的穆罕默德卻沒有得到真主的這種眷顧[339]。穆罕默德的追隨者伊本·勞哈（阿拉伯语：عبد الله بن رواحة）聲稱「即使他沒有顯著的神跡，僅僅是他的存在便表明了祂的旨意」[340]。對於穆罕默德和穆斯林來說，《古蘭經》的所有章節都是真主的神跡，所以《古蘭經》的章節被稱作「阿亞」，意思是奇跡。《古蘭經》經文提出「如果你們是誠實的」，「那末，你們試擬作一章」，向不信者提出了挑戰[341]。
穆罕默德的性癖和婚姻生活一直都是西方反對伊斯蘭教的一方聚焦的議題[410]。他在踏入50歲後迎娶了當時不足10歲的阿伊莎，被指等同虐兒[411]。曾任荷蘭議員的希爾西·阿里稱穆罕默德在當今會被視為戀童，但史學家丹尼絲·斯佩爾伯格（英语：Denise Spellberg）認為阿伊莎的婚齡可能是後世所創，用以說明穆罕默德最寵愛的妻子在結婚時是處女[412][413]。伊斯蘭教法學者賽義德·穆罕默德·雅斯曼（Sayyid Muhammed Jasmin）認為批評穆罕默德娶了年幼的阿伊莎是現在論的說法，以當時並不存在的現代形勢來錯誤解讀歷史[414]。
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关于阿拉伯人名，請見「穆罕默德 (人名)」。
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