Speaking to reporters in Kabul, Karzai did not accuse the Pakistani government of any role in the attack, but he said he would raise the issue with Islamabad as part of Kabul's investigation into the case.
He also said that his intelligence chief, Asadullah Khalid, is recovering from the wounds he sustained in the December 6 attack.
He added that it was not the first time that Afghan authorities believed such a high-profile assassination plot originated in the capital of Pakistan's restive Balochistan Province, citing the killing of high peace council chairman and former President Berhanuddin Rabbani in 2011.
"We will discuss this issue very clearly with Pakistan authorities, to establish what steps they have taken and what they intend to do in regard to these plots which are planned in Quetta, in Pakistan," Karzai said. "The attack against the professor [Rabbani] was planned in Quetta, and now the attack on Asadullah Khan Khalid has also been organized in Pakistan. Therefore this is a very important issue for us and we hope that the Pakistan government in this regard gives us accurate information and cooperates seriously, so that the doubts of the Afghan people are allayed."
The bomber detonated explosives concealed on his body during a meeting with Khalid, similar to the way the killer thwarted tight security in Rabbani's case.
Karzai suggested the method pointed to greater sophistication than Taliban fighters could muster on their own.
"Apparently the Taliban claimed responsibility for the attack, like many other attacks in the past," the president said. "But the reality is that such a complicated attack, and a bomb that was hidden inside his body, is not the work of the Taliban. It's a completely professional and thoroughly engineered type of attack. The Taliban are not capable of that, and therefore there are bigger and professional hands involved in this."
Rising Karzai Ally
Khalid was appointed in September to head Afghanistan's National Directorate of Security.
Ghazni-born Khalid was previously the Karzai government's minister of tribal and border affairs and had served stints as governor of two Afghan provinces.
He has survived previous assassination attempts thought to have been organized by the Taliban.
Khalid's political rise has not been without controversy. Persistent but unproven accusations have followed him of involvement in the illegal drug trade.
Canadian officials have also reportedly cited "numerous and consistent" allegations of human rights abuses by Khalid, including a suggestion that he had personally ordered the killing of five United Nations workers.