In this work, wetting behavior of Ti–20Zr–20Cu–20Ni brazing filler on Ti–6Al–4V substrate was studied using sessile drop technique. Effects of the substrate surface roughness, Ra of ~0.40 and 0.08 µm, and heating scheme on wetting and spreading of the filler metal were evaluated. The wetting mechanism was investigated by the combination of cooling technique, thermal, compositional, and microstructural analysis. This was performed using a heat-flux DSC and an SEM equipped with EDS. The degree of wetting was evaluated by measuring the apparent dynamic contact angle between the filler drop and substrate surface and by calculating the drop spread ratio. The surface roughness of the substrate was found to have little or no effect on the final apparent contact angle. The wetting behavior of this system showed a reactive nature, because it involves dissolution of the substrate and formation of interfacial layers. Three heating schemes were used in the current study. While the high heating rate of 6.8 °C s−1 was found to limit the metallurgical reaction between the substrate and the brazing filler, in the low heating rate scheme of 1.7 °C s−1, more intense metallurgical reaction occurred between the brazing filler and the substrate. The high heating rate with soaking scheme is recommended for brazing, because it entails extensive spreading and limited metallurgical reaction between the brazing filler and the substrate.