Semkow held posts as principal conductor of the National Opera in Warsaw (1959–62), principal conductor of the Royal Danish Opera and the Royal Danish Orchestra in Copenhagen (1966–76), as well as Music Director of the Orchestra of Radio-Televisione Italiana (RAI) in Rome. In the USA, Semkow served as music director of the St. Louis Symphony Orchestra (1975–79), and as music advisor and principal conductor of the Rochester Philharmonic (1985–89). He was a regular guest conductor of the Detroit Symphony Orchestra over a 40-year period, including guest appearances over 24 consecutive seasons from 1986 to 2009.
Semkow lectured on music at the University of Colorado and conducted master classes at Yale University and New York's Manhattan School of Music. He recorded commercially with the St. Louis Symphony Orchestra for the Vox/Turnabout label.