An automatically configurable 2-wire/3-wire serial communications interface (AC23SCI), which includes start-of-sequence (SOS) detection circuitry and sequence processing circuitry, is disclosed. When the SOS detection circuitry is coupled to a 2-wire serial communications bus, the SOS detection circuitry detects an SOS of a received sequence based on a serial data signal and a serial clock signal. When the SOS detection circuitry is coupled to a 3-wire serial communications bus, the SOS detection circuitry detects the SOS of the received sequence based on a chip select (CS) signal. The SOS detection circuitry provides an indication of detection of the SOS to the sequence processing circuitry, which initiates processing of the received sequence using the serial data signal and the serial clock signal upon the detection of the SOS. As such, the AC23SCI automatically configures itself for operation with some 2-wire and some 3-wire serial communications buses without external intervention.