"I strongly condemn the cowardly attack today in Afghanistan," Clinton said.
"My thoughts and prayers are with all those who were injured and the families who lost loved ones."
More than 200 people were wounded in the blast in the main northwestern city of Peshawar, the deadliest in a surge of attacks by suspected insurgents this month. The government blamed militants seeking to avenge an army offensive launched this month against Al Qaeda and Taliban in their stronghold close to the Afghan border.
The bombing was the deadliest since explosions hit homecoming festivities for former Prime Minister Benazir Bhutto in Karachi in October 2007, killing about 150 people. Bhutto was later slain in a separate attack.
Wednesday's bomb destroyed much of the Mina Bazaar in Peshawar's old town, a warren of narrow alleys clogged with stalls and shops selling dresses, toys and cheap jewelry that drew many female shoppers and children in the conservative city.
The blast collapsed buildings, including a mosque, and set scores of shops ablaze. The wounded sat amid burning debris and parts of bodies as a huge plume of gray smoke rose above the city.
Crying for help, men tried to pull survivors from beneath wreckage. One man carried away a baby with a bloody face and a group of men rescued a young boy covered in dust, but others found only bodies of the dead. A two-story building collapsed as firefighters doused it with water, triggering more panic.
"There was a deafening sound and I was like a blind man for a few minutes," said Mohammad Usman, who was wounded in the shoulder. "I heard women and children crying and started to help others. There was the smell of human flesh in the air."