The Murciélago was Lamborghini's first new design in eleven years, and was also the brand's first new model under the ownership of German parent company Audi, which is owned by Volkswagen.

In the Castilian Spanish spoken in most of Spain the word is pronounced [muɾˈθjelaɣo], with a voiceless dental fricative [θ] (as in English thing).

The suspension utilised in the car uses an independent double-wishbone design, and the bodywork mostly features carbon fibre except for the steel roof and aluminium scissor doors.

The interior was also made more comfortable and ergonomic than its predecessor sporting a simple and clean look with all the major controls along with the gearshift knob integrated into the central tunnel.

The 6,192 cc (6.2 L; 377.9 cu in) naturally aspirated V12 engine installed in the first generation cars generated a maximum power output of 580 PS (572 hp; 427 kW) at 7,500 rpm and 650 N⋅m (479 lb⋅ft) of torque at 5,400 rpm, accelerating the car from a stand still to 100 km/h (62 mph) in 3.8 seconds and on to a top speed of 333 km/h (207 mph).

The concept car of the upcoming open-top variant was presented at the 2003 Detroit Motor Show as the Murciélago Barchetta.

The roof which was made of fabric could be folded and fit into a leather bag supplied with the car in order to store it in the front compartment when not in use.

The roadster weighs 29 kg (65 lb) more than the coupé due to the loss of the roof and the addition of chassis reinforcing components.

The new title incorporated the car's name, along with an alphanumeric designation which indicated the engine's orientation (Longitudinale Posteriore), and the updated power output.

Interior seating was also re-configured in order to provide greater headroom, and a new stereo system formed part of the updated dashboard.

Optional equipment included Carbon fibre-reinforced Silicon Carbide (C/SiC) ceramic composite brakes, chrome paddle shifters and a glass engine cover.

[15] At the 2006 Los Angeles Auto Show, Lamborghini announced that the roadster version of the Murciélago would also be updated to LP 640 specifications.

At the 2009 Geneva Motor Show, Lamborghini unveiled a high performance variant of the Murciélago, the LP 670–4 SuperVeloce.

The air intakes were made bigger for better brake cooling and the front spoiler extended much farther for improved downforce.

The engine cover was specially designed for the SV and consisted of three hexagonal plexiglass plates supported by a carbon fibre framework.

[21] According to Maurizio Reggiani, head of Lamborghini R&D at the time, the LP 670–4 SV's steering was tuned for high-speed sensitivity.

The initial plan of 350 units was scrapped due to the factory requiring to make room for the Aventador's assembly line which is the Murcielago's successor.

Enhancements over the standard car included a limited-edition blue body color that was called "Verde Artemis", carbon-fibre exterior detailing, upgraded wheels, a revamped exhaust system, and a numbered plaque on the inside of the rear window.

However, a Murciélago R-GT entered jointly by IPB Spartak Racing and Reiter Engineering finished 8th overall and 5th in the GT1 class in the 2008 24 Hours of Spa.

They finished 2 laps ahead of the lead Corvette to take the second international win for a Lamborghini GT car.

Swiss Racing Team had some points finishes but after a crash between both cars at the Sachsenring round, they had a lack of spare parts and did not compete in the next three events.

Subsequently, the Miura concept was officially debuted at the North American International Auto Show just two weeks later.

The Murciélago is featured on the cover and in the car roster of the racing video game Need For Speed: Hot Pursuit 2.

A Murciélago LP 640 in police livery is also featured in the promotional video of Need For Speed: Hot Pursuit alongside a Pagani Zonda Cinque.