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In this study, the effects of four control parameters, i.e., the cutting speed (vc), feed per tooth (f), depth of cut (ap), and flow rate of the cutting fluid (Q), on the surface roughness (Ra) and cutting force (Fc) were investigated in the slot milling of titanium alloys (Ti-6Al-4V). The effects of the control parameters were determined by a statistical analysis. In addition, RSM models for Ra and Fc during machining under three cooling/lubrication conditions, i.e., dry, flood, and minimum quantity lubrication (MQL), were obtained. The results revealed that both Ra and Fc are sensitive to changes in f, ap and Q. It was found that the MQL condition generates lower values of Ra where the surface roughness value is 0.227 µm. By contrast, Fc values under the MQL condition were close to those of the flood condition and at times even better. The machining performance at a cutting-fluid flow rate of 36 mL/h under the MQL condition was found to be the best under certain machining conditions. MQL was found to be an effective alternative technique for conventional conditions when machining Ti-6Al-4V.