A total of 80 cases of the crippling disease were reported in Afghanistan last year -- a three-fold increase over 2010, the health ministry said, marking a major setback in the drive to eradicate polio worldwide.
About four in five of the cases were in the troubled south of the country, with Karzai pointing to the area along the porous border with Pakistan, marked out by the disputed Durand Line, as particularly hard hit.
The area is a stronghold for hardline Taliban militants, who have waged a 10-year war to oust Karzai's government since they were themselves overthrown by a US-led invasion in 2001.
"Despite all the past efforts to vaccinate millions against polio, there are still children suffering from the disease on both sides of the Durand Line," the president said.
Militants who stood in the way of vaccination teams trying to prevent the spread of the paralysing illness were "the true enemies of our children's future", he said.
Karzai appealed to religious and community leaders to persuade the insurgents to allow the immunisation teams to vaccinate children.
Polio -- which afflicts mainly the under-fives, causing death, paralysis and crippled limbs -- travels easily across borders and is transmitted via the faecal matter of victims.
The news of the increase in Afghan cases comes just days after India announced that it had marked a year since its last case of polio -- a major milestone in a country once considered the epicentre of the disease.
India, Afghanistan, Pakistan and Nigeria are listed by the World Health Organisation as the only four countries where the crippling disease is endemic.
The decline in polio worldwide through a concerted effort by governments, UN agencies and private donors, has raised hopes polio might go the way of smallpox, the only disease successfully eradicated globally.
There were 604 cases of polio worldwide in 2011 and India will only be judged to have eradicated the disease if it stays infection-free for another two years.
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I hope this isn't Pakistan in a couple of years
Yet another reason for Pakistan to close the border with Afghanistan by building a big fence or wall. We have suffered enough due to the refugees and criminals who come to Pakistan from there. Now they are sending over people with polio!