William H. Wisener began his career in law and politics, publishing a pro-Whig newspaper during his early years. He held multiple positions in the Tennessee House of Representatives and Senate, demonstrating a commitment to state governance. Wisener opposed secessionist initiatives and advocated for internal improvements, judicial reform, and tax reduction. His post-Civil War efforts included supporting the Thirteenth Amendment and organizing for Union refugees. Wisener's later career saw him participating in national conventions and running for higher offices, reflecting a sustained engagement in public service and policy advocacy.

William H. Wisener's political career is marked by a blend of unexpected policy alignments and steadfast opposition to divisive issues. His support for the Kansas-Nebraska Act juxtaposes with his lifelong opposition to secession, revealing a complex approach to regional versus national interests. Wisener's advocacy for tax reduction and internal improvements contrasts with his backing of public school funding, showcasing a nuanced fiscal strategy. His unwavering stance against the Ku Klux Klan and commitment to enforcing federal laws highlight a principled yet pragmatic approach to maintaining order and justice.