The result of the British MotoGP was just what 'The Doctor' ordered as it took the legendary Italian back to the top of the MotoGP championship standings ahead of Movistar Yamaha teammate Jorge Lorenzo.
The race also saw a major blow to the title chances of defending champion Marc Marquez of Spain, who occupied pole position but went out at Copse Corner when challenging Rossi for the lead on lap 13.
The Repsol Honda rider now trails Rossi by 77 points with just six rounds remaining of the 2015 season, unable to back up his victory in Indianapolis and runner-up spot behind Lorenzo in the Czech Republic.
The pair had built up a big lead over the chasing pack, with Ducati pair Danilo Petrucci and Andrea Dovizioso the surprise nearest challengers.
Petrucci, who eventually finished a fine second, his first podium in MotoGP, closed to under two seconds with two laps to go, but Rossi responded to win comfortably, his first victory at the Central England circuit and fourth of the season.
Lorenzo, who trails Rossi by 12 points heading into his teammate's home race at Misano, wound up fourth, just ahead of Dani Pedrosa on the second Repsol Honda bike.
Scott Redding took the best result of his MotoGP to be best of the home riders ahead of compatriot Bradley Smith in sixth place.
There was further cheer for British fans when Danny Kent dominated the Moto3 race for his sixth win of the season, while Frenchman Johann Zarco was equally impressive in the Moto2 category for his fifth checkered flag of 2015.