The MIMO-OFDM system fully exploits the advantages of MIMO and OFDM, effectively resisting the channel multipath fading and inter-symbol interference while increasing the data transmission rate. Studies show that it is the principal technical mean for building underwater acoustic networks (UANs) of high performance. As the core, a signal detection algorithm determines the performance and complexity of the MIMO-OFDM system. However, low computational complexity and high performance cannot be achieved simultaneously, especially for UANs with a narrow bandwidth and limited data rate. This paper presents a novel signal detection algorithm based on generalized MMSE. First, we propose a model for the underwater MIMO-OFDM system. Second, we design a signal coding method based on STBC (space-time block coding). Third, we realize the detection algorithm namely GMMSE (generalized minimum mean square error). Finally, we perform a comparison of the algorithm with ZF (Zero Forcing), MMSE (minimum mean square error), and ML (Maximum Likelihood) in terms of the BER (bit error rate) and the CC (computational complexity). The simulation results show that the BER of GMMSE is the lowest one and the CC close to that of ZF, which achieves a tradeoff between the complexity and performance. This work provides essential theoretical and technical support for implementing UANs of high performance.