The riders' championship title was won for the third time by Marc Márquez, after his fifth victory of the season at the Japanese Grand Prix gave him an unassailable lead over his title rivals Lorenzo and Valentino Rossi – who both crashed out at Motegi – with three races remaining. Márquez's title marked a return to the top step for Honda after a difficult 2015 campaign for its factory team. Márquez ultimately won the championship by 49 points.
Reigning champion Lorenzo won three of the first six races to lead the title race, but very poor wet weather form during wet races in mid-season curtailed his title bid along with no wins in the dry until the season-ending race in Valencia. Rossi was the most consistent title challenger, yet he crashed out of three races up until Márquez's decisive victory in Japan. The Yamaha team suffered a severe win drought from June onwards, going eight races without a win before Márquez clinched the title. The drought reached ten races before Lorenzo's Valencian triumph, in his final race for the manufacturer before his move to Ducati in 2017. Rossi clinched the runner-up position by 16 points from Lorenzo, while their performances earned Yamaha the teams' championship, although Honda won the manufacturers' championship. The only rookie in this season was Tito Rabat – who clinched the rookie of the year award. LCR Honda rider, Cal Crutchlow, achieved the top independent rider award; winning races at Brno and Phillip Island and finished in 7th place in the championship with 141 points. Ducati and Suzuki both won at least one race during the season, with Ducati's first win marking the first non Yamaha or Honda win for six years.
^ abAndrea Iannone competed in Friday practice sessions at Misano and Aragón, before being replaced by Michele Pirro. At Misano, Pirro initially competed as a wildcard, but was officially designated as a rider replacement.
^ abDani Pedrosa competed in Friday practice sessions at Motegi, before crashing heavily and fracturing a collarbone. He was replaced by Hiroshi Aoyama for the remainder of the weekend.
Starting in 2016, Michelin has become the series' official tyre supplier following Bridgestone's withdrawal from the category.Dorna have also agreed a rule change to the 2016 regulations to increase the wheel size from 16.5 inches to 17 inches (similar to Moto2 and Moto3).
The previous Factory and Open classes will be merged: every bike must adopt the unified electronic package (ECU and software). Each rider will be able to use up to seven engines in a season, albeit with frozen specifications, and the maximum fuel tank capacity will be 22 litres. Factories without a dry win between 2013 and 2015 will still be allowed to use 12 engines with free development, but in case of a determined number of podiums or wins scored during 2016 the factory will lose these benefits for the next season. Similarly, any manufacturer not scoring a single podium in 2016 will gain those concessions in 2017.
^"Honour roll: the 9 winners - so far". MotoGP.com. Dorna Sports. 30 October 2016. Retrieved 31 October 2016. The only other year in the 68 year history of motorcycle grand prix racing that there were eight different winners in a premier-class season was in 2000, when eight riders won 500cc Grands Prix: Kenny Roberts Jnr, Garry McCoy, Valentino Rossi, Max Biaggi, Alex Barros, Alex Criville, Loris Capirossi and Norick Abe.
^"Free Practice (3) Results". Crash.net. Crash Media Group. 10 September 2016. Retrieved 11 September 2016. Ducati test rider Michele Pirro has a wild-card entry and was seen trying an experimental rear wheel design in FP3.