As nouns the difference between supercomputer and mainframe

is that supercomputer is any computer that has a far greater processing power than others of its day; typically they use more than one core and are housed in large clean rooms with high air flow to permit cooling. Typical uses are weather forecasting, nuclear simulations and animations while mainframe is a large, powerful computer able to manage very many simultaneous tasks and communicate with very many connected terminals; used by large, complex organizations (such as banks and supermarkets) where continuously sustained operation is vital.