Ducati withdrew from Grand Prix racing in the early 1970s, when the 500 cc class was effectively dominated by two-stroke technology incompatible with Ducati's road-going four-stroke identity. The shift to four-stroke regulations in 2002, creating the new MotoGP class, gave Ducati its opportunity to return. Ducati's design heritage centered on 90-degree V-twin engines with desmodromic valve actuation, and the Desmosedici concept extended this to a V4 by pairing two L-twin units side by side. The resulting engine used a twin-pulse firing order — two cylinders firing in close succession, then a gap, then the other two — which became a defining characteristic of the machine's sound and power delivery. Design work began in 2001, and the bike was publicly unveiled at the Italian Grand Prix at Mugello in 2002.
The Desmosedici GP3, ridden by Loris Capirossi and Troy Bayliss, competed across the full 2003 MotoGP season. Capirossi scored the first podium for the machine at the opening round in Japan and took a race win at the Grand Prix of Catalunya. Ducati finished second in the manufacturers' standings in its debut year.
The GP4 and GP5 brought progressive development. The GP5, run with Capirossi and Carlos Checa, benefited from a collaboration with Bridgestone on tire development. Hard compounds suited the Desmosedici's rear-spin characteristics, and Capirossi took wins at Motegi and Sepang in 2005.
The GP6 was a lighter and more powerful evolution, with improved aerodynamics and smoother power delivery designed to improve rideability across all track types. Sete Gibernau partnered Capirossi for the 2006 season. A collision between the two Ducati riders at Barcelona, which left both injured, was the season's dramatic low point. Troy Bayliss, recalled as a substitute for the final round at Valencia, won the race — Ducati's first MotoGP victory for a substitute rider — with Capirossi second, giving Ducati its first MotoGP one-two finish.
For 2007, MotoGP regulations capped engine displacement at 800 cc. Ducati began development work on the GP7 extremely early; by August 2006, twenty 800 cc engines of varying specification had been built. The GP7 debuted at the opening 2007 round in Qatar, where Casey Stoner won immediately. The machine carried a clear top speed advantage throughout the season, attributed to its high-output engine and Bridgestone tires, and Stoner clinched the world championship at Motegi in September 2007 — four rounds before the end of the season — delivering Ducati its first MotoGP title.
The GP8 built on the GP7's foundation with modifications to reduce frame chatter and improve mid-range response. It recorded an official top speed of 343.2 km/h at the 2008 Chinese Grand Prix. The GP9 introduced a carbon fiber chassis, a significant departure from Ducati's traditional steel trellis construction and a feature no other MotoGP team used at the time.
The GP10 returned to a big-bang firing order for the first time since the switch to 800 cc engines, focusing on improved rideability and engine longevity within new usage restrictions. The GP11, raced by Valentino Rossi and Nicky Hayden in 2011, represented Ducati's effort to integrate lessons from Rossi's move from Yamaha.
From 2012, MotoGP raised the displacement limit to 1000 cc. The GP12, unveiled in March 2012, was Ducati's first 1000 cc MotoGP contender. Rossi and Hayden continued as factory riders.
The GP16, introduced in February 2016 with Andrea Dovizioso and Andrea Iannone, marked a renewed competitive rise. At the Austrian Grand Prix that season, Ducati dominated all sessions. Iannone overtook Dovizioso at the final corner of the last lap to take his first MotoGP victory, the first win for Ducati or any manufacturer other than Honda and Yamaha since Stoner's 2010 Australian Grand Prix win for Ducati. Dovizioso won in Malaysia later in the season, his first victory with Ducati.
The Desmosedici GP line established Ducati as a regular front-running presence in MotoGP after the early 2000s regulation change. Its engineering approach — a V4 twin-pulse firing order, desmodromic valve actuation, and progressive adoption of carbon fiber structures — influenced how the broader paddock understood Italian racing motorcycle design. The series also produced a road-legal variant, the Desmosedici RR, delivered in limited quantities from early 2008.