Casey Stoner opened the season as defending champion and won the historic night opener in Qatar, with rookie Jorge Lorenzo starting from pole and finishing second. Stoner and Dani Pedrosa were early contenders, with Lorenzo making his presence immediately felt. Lorenzo took his first MotoGP win in Portugal.
Rossi struck form in China with his first win of the year, then claimed France and Italy to build momentum. Stoner responded with three consecutive victories in Britain, the Netherlands, and Germany, taking pole position and the fastest lap at all three rounds. Heading into the United States Grand Prix at Laguna Seca, Stoner trailed Rossi by only 20 points.
The Laguna Seca race became the turning point of the season. Stoner took pole and led from the start, but Rossi passed him mid-race on the first lap and Stoner could never complete a decisive countermove. On lap 24 Stoner fell at the final corner, remounted, and finished second. Rossi then won five consecutive races, extending his championship lead decisively. Stoner fell while leading in Czech Republic and San Marino, handing Rossi additional victories. Rossi clinched his sixth premier-class title with three races remaining by winning in Japan, with Stoner finishing second.
The Indianapolis Grand Prix, added to the calendar for the first time, was complicated by the passage of Hurricane Ike, which brought cold temperatures, heavy winds, and rain. A battle developed between Rossi and former champion Nicky Hayden, who took his first podium of the season before the race was ended early with Rossi leading.
The season also marked the final year of Michelin as a tyre supplier to the MotoGP class. Bridgestone became the sole tyre supplier from 2009, a status it held until the end of 2015.
The 250cc season opened with KTM and Mika Kallio taking early form, but Marco Simoncelli emerged as the dominant force across the season. Simoncelli ran on a semi-works Aprilia at the start of the year but his performances earned him a full works machine. He went on to win the 250cc World Championship with one round remaining, with Alvaro Bautista finishing second in the standings.
Mike di Meglio won the 125cc World Championship with multiple victories and consistent results. Simone Corsi won three of the first six races and provided the closest challenge, while reigning champion Gabor Talmacsi struggled with reliability issues on his new machine. The season introduced several first-time race winners including Andrea Iannone, Stefan Bradl, Nicolas Terol, and Scott Redding, the latter becoming the youngest winner in the class's history at that time.
The Turkish Grand Prix was removed from the calendar. The Portuguese Grand Prix was moved forward from September to April to fill that vacancy. The Indianapolis Grand Prix joined the schedule for the first time. The United States Grand Prix at Laguna Seca ran for the MotoGP class only, as a Californian air-pollution law prevented the 125cc and 250cc two-stroke machines from competing.
The 2008 season is remembered primarily for the Rossi-Stoner rivalry and the pivotal Laguna Seca race, which many observers regard as one of the defining moments of the 800cc formula. Stoner's fall from the lead under sustained pressure from Rossi crystallised the competitive character of both riders. The season also closed a chapter on Michelin's long involvement in the premier class, transitioning MotoGP to a single-tyre era that would shape competition for the following seven years.