The article provides a systematic analysis of the main points of development of the economic theory of the 20th – early 21st centuries and highlighted such steps along the way as the two-component system, the three-section system, the four-section system, and the six-section system of political economy. On this basis, the author offers an original vision of the creative development of Karl Marx’s methodology in dialectical comparison with the methodology of dominant economic theory (economics), examines the causes and results of Marx’s transition from the plan of six books to the formation of the four volumes of Capital. The author sees the creative development of the methodology and theory of Marxist political economy in taking a step towards the creation of a renewed system of political-economic knowledge that includes the following five main components: ultra-micro economy, micro-economy, meso-economy, macro-economy, cosmic-economy. The ultra-micro-economics focuses on explaining labor and general production, as well as human nature as expressed in individual economic behaviors and economic activities. The micro-economics mainly explains the distribution, production, income and wealth of families; consumption, saving and investment; and population. The meso-economics deals mainly with the development, movement, organization, and division of labor of enterprises; with inter-industry relations; with the division of labor; with the organization and integration of the regional economy; and with the flow of production factors, trade relations, and balanced and non-balanced growth. The macro-economics deals mainly with decision and settlement in relation to national income; with general equilibrium between the product market and currency market; with the models of total demand and total supply and their relationship; with unemployment and inflation; with economic cycles and growth; and with macro-economic regulation. The cosmic-economics mainly explains the international division of labor; production, trade, finance, and resource and wealth distribution; globalization and regionalization; imbalances of economic development; the economic system.