Flem D. Sampson completed his undergraduate and law degrees, subsequently establishing a legal practice and serving as city attorney in Barbourville. He held leadership roles in local banking and water-works companies. Sampson's political career began with his election as county judge, followed by judicial positions in the circuit court and the Kentucky Court of Appeals, where he became chief justice. As governor, he focused on controlling government costs, infrastructure development, and labor disputes, including a notable response to a union miners' strike. Post-governorship, he returned to legal practice and held advisory roles in highway development.

Flem D. Sampson's political career is marked by an intriguing blend of fiscal conservatism and industrial pragmatism. Despite advocating for cost control during the Great Depression, Sampson endorsed extensive highway construction, revealing a selective approach to economic priorities. His support for damming the Cumberland Falls for hydroelectric power, despite environmental opposition, highlights a willingness to balance regional economic benefits against ecological concerns. Sampson's legislative record also shows an unexpected convergence with opposing factions on environmental regulations, revealing a highly calculated approach to protecting regional industrial interests.