She reached the milestone in a roll call vote from all 50 states at the Democratic National Convention.
Mrs Clinton’s nomination comes after Senator Bernie Sanders’ supporters disrupted the first day of the convention with boos and jeers.
Party officials have worked to ease tensions amid protest on the floor.
Mrs Clinton passed the 2,382 delegates needed to claim the nomination after South Dakota announced its delegate vote count.
In a symbolic gesture of party unity, former Democratic rival Senator Bernie Sanders took the microphone to move to suspend the procedural rules and declare Mrs Clinton as the nominee.
Chair of the Democratic National Committee, Congresswoman Marcia Fudge, approved the move after a unanimous voice vote and members of the crowd erupted into cheers as they held up new Clinton signs.