The new leader faces intense pressure to tackle rising Islamist extremism and deep economic troubles.
Zardari, 53, was sworn in by the country's top judge at a ceremony in the presidential palace, broadcast on national TV.
The ceremony was attended by Afghan President Hamid Karzai, who has criticized Pakistan for failing to bring Taliban militants based near the Afghan border under control.
Zardari won a parliamentary vote on Saturday, and replaces former army general Pervez Musharraf, who resigned as president on August 18 to avoid impeachment by the ruling government coalition.
Zardari's Pakistan People's party had led the coalition to victory in the February election.
The new leader, whose wife was shot dead in December 2007 during a campaign rally in Rawalpindi, has said he also expects to be targeted by extremists.
He is due to give a news conference later on Tuesday.
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