The LP640 Roadster version was first shown at the Geneva Motor Show in March 2006, as a facelift for the coupé version. There were also a few minor external changes, primarily to the low air intakes. The front and rear bumpers have been reshaped to channel air more efficiently, and the new exhaust has been shaped into the rear diffuser to minimize aerodynamic lift. The air intake on the left side has been enlarged to accommodate the feeding of the oil cooler. The car's body is made up of steel and carbon fiber, while underneath a revised suspension has been added to keep up with the car's exceptional performance. The LP640 Roadster retains the original car's scissor-opening doors.

The Murcielago LP640 Roadster features a 6.5 L engine, now producing 640 bhp, improving performance substantially. Like the base Murciélago, the engine is mounted "backwards", with the transmission in front of the engine and the differential behind it, instead of a transaxle normally seen on mid-engine cars. It also has an all-wheel-drive system that normally distributes 70% of the torque to the rear wheels, but can allocate up to 100% to either end depending on where the grip is running out. There are also new 18-inch Hermera alloy wheels running huge 335/30 tires at the rear.