This work presents an airfoil parameterization method, called hybrid b-spline–targets (HBT), that enables a human designer or an optimization algorithm to separately control airfoil overall thickness, nose radius, camber distribution, and thickness distribution, while at the same time preserving a standard b-spline representation of the airfoil lower and upper surface in a CAD system, by means of a parameter transformation external to the CAD system. The parametrization methodology, transformation between HBT and b-spline parameters, and an optimization demonstration on a transonic wing-body transport aircraft configuration with RANS flow modeling are presented.