The Spaniard (Yamaha) claimed his fifth victory in nine rounds this season after finishing over five seconds clear of countryman Dani Pedrosa (Repsol Honda), with Italian Andrea Dovizioso third on his Monster Yamaha.
The triumph means Lorenzo, who was also victorious at Mugello last year, now has 185 points in the overall standings at the midway point of the season, 19 clear of second-placed Pedrosa.
Reigning champion Casey Stoner of Australia, who has three victories to his name this season but could only finish eighth, is in third spot on 148 points, with Dovizioso's fourth in 108.
Britain's Cal Crutchlow, who came home sixth on his Monster Yamaha, is fifth overall on 95.
Lorenzo, the 2010 world champion, said: "From the beginning I felt great on this track, the asphalt was completely different to Sachsenring (German Grand Prix) which was a nightmare for us.
"From the first practice here I felt very strong, very good on the bike and a fast constant pace.
"It's been a great win for the whole team's efforts and for Yamaha who have given me such a good bike."
Pedrosa, who was victorious last time out in Germany and earned pole position for today's race with a track record lap yesterday, praised his compatriot for his win.
"He was riding very strong so I have to congratulate him, finally for me a second place is a good result overall and I want to thank all the team for their hard work this weekend," Pedrosa said.
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A disappointed Stoner said: "It's definitely not the way we planned it, we thought today we could be fighting for the podium and maybe have the pace to stay with Dani.
"Jorge has ridden fantastically all weekend and hasn't really put a foot wrong but I think a third position would have been good today. However, we just couldn't get the bike working."