This paper presents an assessment of the potential fuel burn savings offered by the transonic strut-braced-wing configuration within the single-aisle class of aircraft relative to a modern conventional tube-and-wing aircraft through aerodynamic shape optimization based on the Reynolds-averaged Navier–Stokes equations. A representative strut-braced-wing aircraft is first developed through conceptual multidisciplinary design optimization based on the Airbus A320neo, with current technology levels assumed. A concept for the conventional tube-and-wing configuration is also developed to represent the Airbus A320neo as a performance baseline. Single-point aerodynamic shape optimization is then performed on wing–body–tail models of each aircraft to address aerodynamic design challenges and to provide more accurate performance estimates. Results indicate that shock formation can be mitigated from the wing–strut junction of the strut-braced wing at Mach 0.78 and a relatively high design lift coefficient of 0.750, providing an 8.2% reduction in block fuel over a 1000 n mile nominal mission when compared to the conventional tube-and-wing aircraft. Multipoint aerodynamic shape optimization is then performed to build toward a more credible estimate of fuel burn performance, with results showing a reduction in the fuel burn savings to 7.8% at the nominal design point relative to the conventional tube-and-wing aircraft to maintain a 7.6–8.0% improvement over the envelope of operating conditions, which includes design points at even higher Mach numbers and lift coefficients. These results demonstrate the viability of the transonic strut-braced-wing configuration for transport aircraft within the single-aisle class and its potential for reducing commercial fleet fuel burn.