The 250 GT/L Lusso used a Colombo-designed V12 engine with a displacement of . This engine developed an output of at 7,500 rpm and torque at 5,500 rpm. It was able attain a maximum speed of , thus becoming the fastest passenger car of that period, and required only 7 to 8 seconds to accelerate from . Certain components such as the valves and the crankshaft, were derived from the engine of the 250 GT SWB, while others, such as the pistons and the cylinder block, were derived from the 250 GTE.
