The National Bank of Greece was founded in Athens as a response to the emerging economic needs of the newly independent Greek state. Following the Greek War of Independence against Ottoman rule, the political landscape required a robust financial institution to help stabilize and grow the economy. The establishment of the bank was part of broader efforts to modernize Greece and enhance its economic infrastructure. The founders sought to create an institution that could facilitate credit, promote trade, and eventually foster industrial advancement in the country.

Operation began under the direction of influential figures in Greek finance and politics. The bank was tasked with issuing banknotes, managing public deposits, and providing loans to support merchant activities. Its charter allowed it to extend credit to government projects, thereby becoming an essential player in national development plans. The creation of the bank was also symbolic of Greece's aspirations for financial autonomy and its vision of building a self-sustaining economy.

Initially, the bank faced various challenges, including limited resources and a nascent market. Nonetheless, over time, it adapted and expanded its operations. The National Bank of Greece not only supported the local economy but also established connections with international financial systems, marking Greece's re-entry into the global economic framework. By promoting trade and development initiatives, the bank significantly contributed to the modernization of the Greek economy throughout the 19th and into the early 20th centuries.