We present an experimental and theoretical study of slip nucleation in high entropy FeNiCoCrMn alloy which possesses superb mechanical properties. Uniaxial compression experiments were conducted on the View the MathML source59¯1 oriented single crystals. The single crystals permit evaluation of critical resolved shear stress (CRSS), and using Digital Image Correlation strain measurements it is possible to track the slip nucleation precisely. The experimental value of 175 MPa for CRSS is in excellent agreement with 178 MPa obtained utilizing an advanced atomistic-modified Peierls–Nabarro modeling formalism. This close agreement demonstrates the efficacy of our methodology and has implications in design of new high entropy alloys.