Nearly 7,000 US marines and Afghan forces entered the farmlands and the main city of Marjah, a volatile district in southern Helmand province, while thousands more including British troops entered the Nad Ali district of central Helmand.
Karzai called upon "all Afghan Taliban to use this as an opportunity to renounce violence and re-integrate into civilian life alongside other Afghans for the welfare of their country".
NATO officials have said the reason that the operation was flagged for weeks was to let the militants flee the area or put down their arms.
The joint forces killed five Taliban insurgents and injured eight others when they targeted 13 locations in early hours of Saturday, Daoud Ahmadi, spokesman for the Helmand's governor said.
He said the forces had "significant advance in the first hours," but the large number of roadside bombs planted in and around the main town slowed their progress.
Karzai also called on Afghan and NATO troops to "to exercise absolute caution to avoid harming civilians" and "consult the local people, fully coordinate their actions and to avoid using air power in areas where civilians can be at risk."
Wary of the delicate issue of civilian casualties, NATO officials had publicly talked about the operation for months in order to inform the civilians of the looming peril.
Days prior to the operation, hundreds of residents of Marjah left the district for Lashkargah, the provincial capital, but some said that most of the 80,000 population had stayed put because they could not afford to move or did not want to leave everything behind.
A total of 15,000 troops including US, Afghan, British, Canadian, Danish and Estonian personnel were mobilised for the operation, dubbed 'Mushtarak', a Dari word for "together".
