During her three-day trip Mrs Clinton hoped to strengthen ties between the US and Pakistan and tried to address a rising tide of anti-American feeling.
In an interview with the BBC she urged Pakistanis to "realise the connection" between al-Qaeda and the Taliban.
But her arrival was overshadowed by a deadly bombing in the city of Peshawar.
More than 100 people died when a car bomb exploded in a busy market on Wednesday.
The BBC's Jill McGivering says that a great deal of anger in Pakistan is focused on the US - widely seen as interfering and destabilising Pakistan for its own ends.
Mrs Clinton acknowledged there was what she called a trust deficit towards the United States in Pakistan because of past policies.
But she said she was working to change that by reaching out to ordinary Pakistanis.
Mrs Clinton is due in the Middle East at the weekend to meet Israeli Prime Minister Benjamin Netanyahu and Palestinian Authority President Mahmoud Abbas.
Susan Collins gives kudos to Hillary for calling out Pakistan on Al Qaeda: