Maximum likelihood sequence estimation (MLSE) is an optimal solution to realize sequence detection in the digital signal processing (DSP) of short reach O-band intensity modulation/direct detection (IM/DD) systems with bandwidth limitation. However, traditional MLSE requires relatively high computational complexity for short reach optical interconnect. Although the computational complexity of single-symbol sequence detection is quite low, the capability of combating with the inter symbol interference (ISI) is inadequate. To combine the low computational complexity of single-symbol sequence detection with the high reliability of multi-symbol sequence detection in MLSE, decision region partition aided MLSE (DRP-MLSE) is proposed and verified with 60-Gbaud and 65-Gbaud PAM-4 IM/DD systems over 40-km single-mode fiber (SMF) transmission. The experimental results show that the DRP-MLSE can realize similar performance of conventional MLSE with negligible penalty and significantly lower computational complexity.