Pavel Kysilka is a graduate of the University of Economics in Prague. Between 1986 and 1990, he worked at the Institute of Economics of the Czechoslovak Academy of Sciences, and from 1990 to 1991 served as Chief Advisor to the Minister for Economic Policy. During the 1990s, he held the positions of Vice-Governor and Executive Governor of the Czech National Bank (CNB), where he was responsible for preparing and executing the split of the Czechoslovak currency and the introduction of the Czech koruna.

From 1994 to 1997, he served as an expert for the International Monetary Fund (IMF), participating in the introduction of national currencies across several Eastern European countries. In the 1990s, he also served as President of the Czech Economic Society. In 2000, he joined Česká spořitelna as Chief Economist, was elected to the Executive Board in 2004, and served as Chief Executive Officer (CEO) and Chairman of the Executive Board for five years starting January 1, 2011. He was named Banker of the Year three times—in 2011, 2012, and 2013.

Pavel Kysilka is the founder of the glassmaking gallery Galerie na Milovské huti and the associated Milofiori Endowment Fund. He serves as President of the Smetana's Litomyšl Festival, co-founder of the Czech Philharmonic Support Foundation, Vice-Chairman of the Board of the Brno Philharmonic and the Board of Trustees of the Leoš Janáček Foundation, Chairman of the Czech Chamber Music Society, and a member of the Supervisory Board of the Good Angel (Dobrý Anděl) charity.