A staunch loyalist of Prime Minister Nawaz Sharif but with no power base of his own, Hussain's time in office will cement Pakistan's democratic transition back to a ceremonial head of state.
He will formally preside over a government that must solve a power crisis, kick-start the economy, counter a Taliban insurgency and navigate a tricky alliance with the United States.
Often photographed smiling, the 73-year-old Hussain -- who sports a cropped moustache -- has spent most of his life as a key member of the business community in Karachi.
In 1999, Sharif surprisingly appointed him governor of the southern province Sindh, of which Karachi is the capital. But his tenure was cut short when Sharif was deposed in a military coup.
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Hussain was a key figure in Karachi for Sharif, whose Pakistan Muslim League-N (PML-N) party is rooted further north in Punjab.
"He is a selfless and straight-forward man who makes friendship out of sincerity not of utility," Tariq Khaliq, a friend of Hussain's for more than half a century, has said.
Born in Agra, home of the Taj Mahal, in 1940, he was still a child when he fled with his family to Karachi after the 1947 partition of the sub-continent into two separate countries when British colonial rule ended.
He studied at Pakistan's prestigious Institute of Business Administration in Karachi and inherited his family's modest cloth business, which he exported and traded in the local market.
He served as a secretary of the PML-N in Karachi, but his appointment as Sindh governor was considered something of a surprise in political circles.
Hussain was elected president on July 30 by members of the four provincial assemblies and the federal parliament.
He won 432 votes and his only rival, Wajihuddin Ahmed, 77, after the main opposition Pakistan People's Party boycotted the vote.