美国第一夫人（英语：First Lady of the United States），是美国白宫的女主人，通常是指现任美国总统的妻子。不过，若该总统是单身汉或鳏夫，或这总统的妻子未能胜任第一夫人的光环，第一夫人的职位就可能会改由总统的女性亲戚或朋友担任。

现任美国第一夫人为总统巴拉克·奥巴马妻子米歇尔·奥巴马。

美国第一夫人的对应词是美国第二夫人，即美国副总统夫人。现任美国第二夫人是副总统乔·拜登妻子吉尔·拜登。

The First Lady of the United States (FLOTUS), is an unofficial title and position traditionally held by the wife of the president, concurrent with his term of office.

The position of the First Lady is unofficial and carries no official duties. The role of the First Lady has evolved over the centuries. The main role of the First ladies, besides their private role as spouse, has been as host and organizer to the White House. She organizes and attends official ceremonies and functions of state either along with, or in place of, the president.