In this paper, we propose a new differential MIMO single-carrier system with frequency-domain equalization (SC-FDE) aided by the insertion of cyclic prefix. This block transmission system not only inherits all the merits of the SISO SC-FDE system, but is also equipped with a differential space-time block coding (DSTBC) such as to combat the fast-changing frequency selective fading channels without the needs to estimate and then compensate the channel effects. Hence, for practical applications, it has the additional merits of decoding simplicity and robustness against high mobility transmission environments. Computer simulations show that the proposed system can provide diversity benefit as the non-differential system does, while greatly reducing the receiver complexity.