Yousafzai, who at 17 became the youngest Nobel peace prize winner ever in 2014 and was herself shot by the Pakistani Taliban in 2011 for promoting female education, said she was heartbroken.
“I am heartbroken by this senseless and cold blooded act of terror in Peshawar that is unfolding before us,” she said in a statement.
“Innocent children in their school have no place in horror such as this,” the teenaged global icon said.
“I condemn these atrocious and cowardly acts, and stand united with the government and armed forces of Pakistan whose efforts so far to address this horrific event are commendable,” she said.
“I, along with millions of others around the world, mourn these children, my brothers and sisters – but we will never be defeated,” she added.
Indian child rights activist, Kailash Satyarthi, who shared the 2014 Nobel with Yousafzai, termed the attack as “one of the darkest days of humanity.”
“My heart bleeds for the bereaved families. One of the darkest days of humanity,” Satyarthi tweeted.
“These are all our children who’ve been murdered today. My prayers and condolences are with the families,” he said.
“Children are the first casualty of violence and war. It is time we all came together and put a stop to this violence,” he added.
Pakistan's Prime Minister Nawaz Sharif has called for three days of national mourning.
"I feel that until and unless this country is cleansed from terrorism, this war and effort will not stop, no one should be doubtful of this. We have also spoken to Afghanistan about this and we will fight terrorism together," the local Pakistani daily Dawn quoted Sharif as saying when he landed in Peshawar Tuesday evening.
Afghan president Ashraf Ghani termed the school attack as un-Islamic.
“I strongly condemn killing of innocent and cherubic children which is an inhumane, un-Islamic and barbaric,” Ghani said in a statement.
Indian Prime Minister Narendra Modi was one of the first South Asian leaders to react to the unfolding tragedy in neighboring Pakistan.
“It is a senseless act of unspeakable brutality that has claimed lives of the most innocent of human beings – young children in their school,” Modi tweeted.
“My heart goes out to everyone who lost their loved ones today. We share their pain and offer our deepest condolences,” he added.
Senior Kashmiri leader Mirwaiz Umar Farooq condemned the Peshawar attack.
"It is in every way an inhuman and condemnable act, and it is doubtlessly against the spirit of humanity and Islam, and there is no space in Islam for such an act," said Farooq.
The Kashmiri leader is chairman of the All Parties Hurriyat Conference and cleric of Srinagar's Grand Mosque in Indian-held Kashmir. He called for an in-absentia funeral prayers for the slain Pakistani children at his mosque in Srinagar Wednesday.
U.N. Secretary-General Ban Ki-moon condemned the attack as "an act of horror and rank cowardice to attack defenseless children while they learn."
"No cause can justify such brutality. No grievance can excuse such horror," Ban said. "Getting an education is every child's right. Going to school should not have to be an act of bravery."
U.K. Prime Minister David Cameron said he was deeply shocked by the incident.
“The news from Pakistan is deeply shocking. It’s horrifying that children are being killed simply for going to school,” Cameron tweeted.
French President Francois Hollande condemned the brutal attack with “utmost firmness”.
“No words can describe the abjection of such an attack against children in their school,” Hollande said in a statement.
“France stands alongside the victims and their parents. It supports the Government of Pakistan in the fight against terrorism,” he said.
“The United States strongly condemns senseless and inhumane attacks on innocent students and educators, and stands in solidarity with the people of Pakistan, and all who fight the menace of terrorism,” U.S. ambassador to Pakistan Richard Olson also said.
"By targeting students and teachers in this heinous attack, terrorists have once again shown their depravity," Obama said in the statement released by the White House.
U.S. Secretary of State John Kerry said Taliban attack had angered the world.
"The news of the brazen murder of more than 120 innocent students in Peshawar is devastating," he told reporters. "This morning, wherever you live, wherever you are, those are our children and this is the world's loss.
"This act of terror angers and shakes all people of conscience ... the perpetrators must be brought to justice."