The political significance of the Constitution's Supremacy Clause lies in its establishment that the Constitution and federal laws take precedence over state laws. This clause ensures a uniform legal framework across the nation, promoting national unity and stability. It enables the federal government to enforce laws and treaties consistently, preventing conflicts between state and federal jurisdictions. Understanding the Supremacy Clause is critical for interpreting legal disputes and maintaining the integrity of the federal system, ultimately shaping the balance of power in the United States.