Generalized frequency division multiplexing (GFDM) is considered a nonorthogonal waveform and can cause difficulties when used in the spatial multiplexing mode of a multiple-input-multiple-output (MIMO) scenario. In this paper, a class of GFDM prototype filters, in which the GFDM system is free from inter subcarrier interference, is investigated, enabling frequency-domain decoupling during processing at the GFDM receiver. An efficient MIMO-GFDM detection method based on depth-first sphere decoding is subsequently proposed with this class of filters. Numerical results confirm a significant reduction in complexity, especially when the number of subcarriers is large, compared with existing methods.