While still an undergraduate he began his collaboration with TsAGI (Central Aerohydrodynamics Institute in Zhukovsky) where he conducted research on experimental and theoretical thermodynamics of air-to-air and surface-to-air missiles until 1958.

In 1958, following an invitation by academician Georgy Petrov, Ryzhov joins the Keldysh Research Centre (at the time known as NII-1); here his work focused on high speed aerodynamics.

In 1961-1992 and since 1999 he has worked at the Moscow Aviation Institute: docent, professor, pro-rector, rector (1986-1992), head of the aerodynamics department since 2003.

According to the Soviet and Russian journalist and statesman Mikhail Poltoranin, Ryzhov was offered the post of Prime Minister during Boris Yeltsin's time in office, but had turned it down.

Yuri Ryzhov's main works are in the fields of supersonic aerodynamics, rarefied-gas dynamics, interaction of atomic scale particles with surfaces, non-equilibrium processes in gas flows, non-stationary heat transfer.