He said it's needed regardless of Pakistan's views about its rival, India, or its rocky ties with the U.S.
Islamist insurgents use the border area to stage attacks in Afghanistan.
Karzai's spoke Tuesday in interviews with Afghan television stations.
Relations cooled over Afghanistan's signing of a strategic partnership with India and because of Pakistan's anger at the United States, which backs the Karzai government.
Karzai also denied that he wants Afghanistan to become a parliamentary system with a president and prime minister. That counters rumors that he is seeking a way to stay in power -- perhaps as prime minister -- beyond 2014, when he is required to step down.