Asfandyar Wali Khan joined the opposition to Ayub Khan as a student activist. In 1975, he was imprisoned and tortured by the government of Zulfiqar Ali Bhutto and convicted as part of the Hyderabad tribunal for 15 years.Released in 1978, he stayed away from electoral politics till 1990..
Asfandyar Wali Khan served as leader of the Pakhtun Student Federation prior to being elected to the provincial Assembly in the 1990 election, while in the 1993 election he was elected to Pakistan's National Assembly. A seat to which he was re-elected to the National Assembly in the 1997 election and served as Parliamentary leader of the ANP and Chairman of the standing committee on inter-provincial co-ordination.
In 1999, he was elected party president for the first time. He was defeated in the 2002 election, in what was a repeat of his father's defeat in 1990, when a tactical alliance was formed by all the anti-ANP groups against him. After his defeat he resigned as President of his party, only to be re-elected unopposed in the subsequent party election. In 2003 he was elected to the Senate as Senator for a 6 year term. He was re-elected to the National Assembly in the parliamentary elections that was held on February 2008, leading his party to power both provincially and nationally, the former for the first time since 1947 and the latter since 1997.
In September 2008, he was elected as Chairman of the standing committee on foreign Affairs.
In 2008 it was reported by Dawn that he made a secret visit to the United States in which he made high level contacts with the U.S Central Command.
Asfandyar Wali Khan is a democratic socialist and the current the President of the Awami National Party in Pakistan. His father, Khan Abdul Wali Khan, was the party’s first President.