This paper studies the Mach number effect on cruise performance for a 2D Co-Flow Jet (CFJ) airfoil at freestream Mach number of 0.15, 0.30, 0.46 and 0.5. The optimized 2D CFJ airfoil, CFJ6421-SST150-SUC247-INJ117 is redesigned by enlarging the size of the injection and suction slot from the CFJ airfoil previously designed by Lefebvre and Zha. The results show that the best CFJ airfoil corrected aerodynamic efficiency ((CL /CD )c ) occurs at M∞ of 0.30, which produces a (CL /CD )c of 81.04 at Cµ of 0.03 and AoA of 6◦ . The case at M∞ of 0.30 has higher compressibility than that at M∞ of 0.15, but is still far from the sonic speed. The favorable conditions hence provide the optimum aerodynamic efficiency. At the same Cµ and AoA, the maximum Mach number on the CFJ airfoil suction surface at M∞ of 0.15, 0.30, 0.46, 0.50 is 0.264, 0.558, 1.025 and 1.289 respectively. For the case of M∞ of 0.50, the flow becomes transonic. As the M∞ increases, the CL is also increased due to the stronger compressibility effect that creates a greater suction effect. At M∞ of 0.46, which is the critical Mach number for the airfoil at AoA of 6◦, the corrected aerodynamic efficiency is still very good. But when the M∞ is increased to 0.5, the optimum aerodynamic efficiency occurs at a lower AoA and Cµ with AoA = 2◦ and Cµ = 0.01. Under this condition, the flow remain subsonic without shock wave. For the optimum cruise condition with the Mach number varying from 0.15 to 0.5, the ratio of the injection jet velocity to the freestream velocity is varied from 1.24 to 0.68, and the total pressure ratio between the injection and suction slot is from 1.02 to 1.20. The low CFJ jet velocity is beneficial to reduce the noise and the low total pressure ratio is beneficial to achieve the low power requirement at cruise. Comparing the optimum efficiency point of the baseline NACA 6421 airfoil and CFJ airfoil, the CFJ airfoil improves the lift coefficient by 30%. The aerodynamic efficiency is improved by 60% or more (under 100% pump efficiency) and 40% or more (under 70% pump efficiency). This paper also studies two control laws for cruise control of the CFJ airfoil when the AoA varies: One is to achieve constant injection momentum coefficient, the other is to achieve constant injection total pressure. The latter is preferred for its easier sensor measurement, higher airfoil efficiency, and higher stall AoA. The numerical simulations employ the intensively validated in house FASIP CFD code, which utilizes a 3D RANS solver with Spalart-Allmaras (S-A) turbulence model, 3rd order WENO scheme for the inviscid fluxes, and 2nd order central differencing for the viscous terms.