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Political science is methodologically diverse; political scientists approach the study of politics from a host of different ontological orientations and with a variety of different tools. Because political science is essentially a study of human behaviour, in all aspects of politics, observations in controlled environments are often challenging to reproduce or duplicate, though experimental methods are increasingly common (see experimental political science).[28] Citing this difficulty, former American Political Science Association President Lawrence Lowell once said "We are limited by the impossibility of experiment. Politics is an observational, not an experimental science."[17] Because of this, political scientists have historically observed political elites, institutions, and individual or group behaviour in order to identify patterns, draw generalizations, and build theories of politics.

Like all social sciences, political science faces the difficulty of observing human actors that can only be partially observed and who have the capacity for making conscious choices, unlike other subjects such as non-human organisms in biology or inanimate objects as in physics. Despite the complexities, contemporary political science has progressed by adopting a variety of methods and theoretical approaches to understanding politics, and methodological pluralism is a defining feature of contemporary political science.

Empirical political science methods include the use of field experiments,[29] surveys and survey experiments,[30] case studies,[31] process tracing,[32][33] historical and institutional analysis,[34] ethnography,[35] participant observation,[36] and interview research.[37]

Political scientists also use and develop theoretical tools like game theory and agent-based models to study a host of political systems and situations.[38]

Political theorists approach theories of political phenomena with a similar diversity of positions and tools, including feminist political theory, historical analysis associated with the Cambridge school, and Straussian approaches.

Political science may overlap with topics of study that are the traditional focuses of other social sciences—for example, when sociological norms or psychological biases are connected to political phenomena. In these cases, political science may either inherit their methods of study or develop a contrasting approach.[39] For example, Lisa Wedeen has argued that political science's approach to the idea of culture, originating with Gabriel Almond and Sidney Verba and exemplified by authors like Samuel P. Huntington, could benefit from aligning more closely with the study of culture in anthropology.[39] In turn, methodologies that are developed within political science may influence how researchers in other fields, like public health, conceive of and approach political processes and policies.[40]