We report high-performance GaSb-based interband cascade lasers (ICLs) with a top hybrid cladding and operating around 3.5 μm at room temperature. Unlike the conventional superlattice (SL) claddings in GaSb-based ICLs, the top cladding of the present ICLs consisted of an n-SL, followed by an n+-InAs0.91Sb0.09 layer, while their bottom claddings entirely consisted of an n-SL. This “asymmetric” waveguide design is potentially advantageous, since it improves the active-core optical confinement factor, as well as the overall thermal conductance, especially for epitaxial-side-down mounted devices. When operated in pulsed mode, the broad-area ICL featured a characteristic temperature of 57 K and a threshold current density as low as 95 A/cm2 at 25 °C, which is the lowest ever reported for an ICL operating at a similar temperature. The narrow-ridge device processed from the same wafer, operated in continuous-wave (CW) mode up to a temperature as high as 100 °C, with a CW threshold current density of only 150 A/cm2 at 20 °C, although the current leakage was appreciable at the sidewalls.