Seventy-year-old Seif, who hails from Damascus, won 58 votes from the Istanbul-based National Coalition's 102 members, beating out the younger Khaled Khoja.
Born into a family of modest means in Damascus, he began working in a textiles factory aged 12, before eventually opening his own workshop, which later became a profitable factory.
Seif served as a parliamentarian under both Syrian President Bashar al-Assad and his father Hafez before him, and is one of the few lawmakers to have openly criticised the regime and its economic policies.
When the National Coalition was formed later on that year, Seif served as its vice president.
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In his new role, he will replace current head Anas al- Abdeh, who was elected in March 2016.
National Coalition members also elected Abdulrahman Mustafa and Salwa Ktaw as vice presidents.
Syria's war began in 2011 with widespread demonstrations against the Assad government, which responded with a brutal crackdown.