A 850 nm single-mode vertical cavity surface emitting laser (VCSEL)-based data transmission is demonstrated, enabling four-level pulse amplitude modulation (PAM-4) at 64  Gbit/s over 100–300 m in an OM4 multi-mode fiber (MMF). By optimizing the bias of the single-mode VCSEL with a differential resistance of 159 Ω, the related electrical return loss of −5.7  dB is determined to provide an analog modulation bandwidth of 18.9 GHz. After pre-emphasizing the waveform of the PAM-4 format, the PAM-4 data stream can be successfully delivered by the single-mode VCSEL at 64  Gbit/s under back-to-back and 100 m long OM4 MMF conditions. Lengthening the transmission distance worsens the signal-to-noise ratio (SNR) of PAM-4 data to the FEC criterion, as the waveform pre-emphasis of the PAM-4 data stream inevitably induces spectral power compensation from low to high frequencies. Therefore, increasing the OM4 MMF distance from 200 to 300 m significantly reduces the peak-to-peak amplitude of data to suppress the SNR and reduce the transmission capacity from 52 to 48  Gbit/s.