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The 23-year-old, who in an unusual celebration got off his bike and walked on to a neighbouring golf course to take a putt which he needed two to hole, beat home compatriot and pole sitter Dani Pedrosa on a Honda while Australia's former world champion Casey Stoner was third.
Lorenzo took the lead from pole sitter Pedrosa on the first of the 22 laps as five riders battled for the top three in the opening exchanges including Stoner while nine-time champion Valentino Rossi was adrift in eighth.
Italian Andrea Dovizioso was the first of the front five to crack as he came to grief in the middle of the track on the fourth lap and was extremely fortunate not to suffer a serious injury by being hit by one of the oncoming bikes.
The Repsol rider - winner this season of the British MotoGp - resumed the race but tailed off in last place and eventually gave up the ghost and pulled into his stable.
"I don't know exactly what happened," said the 24-year-old Italian, who was 125cc world champion in 2004.
"There was a lot of wind so that explains the slower times out there. I made one mistake as I really pushed hard at the beginning to keep in touch with Lorenzo and Pedrosa.
"However, I am really angry because the way the race has panned out I think we would have been really challenging for second or third place."
Both Lorenzo and his compatriot Pedrosa slowly started to open a gap on third placed American rookie Ben Spies and Stoner, who was also cast adrift by the young American.
The Spanish duo had a lead of over four seconds over Spies and Stoner while that pair had a sizeable lead over a group including fifth placed Rossi, who was some nine seconds adrift along with Nicky Hayden with 12 laps to go.
Stoner stoically had stuck to his task and passed Spies to take third place with 11 laps remaining and it was at this point that Lorenzo wound up the pressure on Pedrosa opening a gap of over a second on him with 10 laps remaining.
Pedrosa was unable to peg him back and Lorenzo ended up coasting to victory and ever nearer to his first MotoGp world title.
Results from the Czech Grand Prix (with rider, country, team and time):
MotoGP
1. Jorge Lorenzo, Spain, Yamaha, 43 minutes, 22.638 seconds.
2. Dani Pedrosa, Spain, Honda, 43:28.132.
3. Casey Stoner, Australia, Ducati, 43:34.064.
4. Ben Spies, United States, Yamaha, 43:36.361.
5. Valentino Rossi, Italy, Yamaha, 43:40.568.
6. Nicky Hayden, United States, Ducati, 43:49.453.
7. Colin Edwards, United States, Yamaha, 43:56.034.
8. Marco Melandri, Italy, Honda, 44:02.044.
9. Hector Barbera, Spain, Ducati, 44:02.277.
10. Randy de Puniet, France, Honda, 44:03.531.
Standings (After 10 of 18 races)
1. Jorge Lorenzo, Spain, Yamaha, 235 points.
2. Dani Pedrosa, Spain, Honda, 158.
3. Casey Stoner, Australia, Ducati, 119.
4. Andrea Dovizioso, Italy, Honda, 115.
5. Valentino Rossi, Italy, Yamaha, 101.
250cc
1. Toni Elias, Spain, Moriwaki, 41 minutes, 51.715 seconds.
2. Yuki Takahashi, Japan, Tech 3, 41:54.027.
3. Andrea Iannone, Italy, Speed Up, 41:54.674.
4. Jules Cluzel, France, Suter, 41:58.620.
5. Julian Simon, Spain, Suter, 41:58.689.
6. Gabor Talmacsi, Hungary, Speed Up, 41:58.739.
7. Alex Debon, Spain, FTR, 41:59.523.
8. Simone Corsi, Italy, Motobi, 42:03.406.
9. Stefan Bradl, Germany, Suter, 42:07.673.
10. Shoya Tomizawa, Japan, Suter, 42:07.689.
Standings (After 9 of 18 races)
1. Toni Elias, Spain, Moriwaki, 161 points.
2. Andrea Iannone, Italy, Speed Up, 106.
3. Thomas Luthi, Switzerland, Moriwaki, 99.
4. Julian Simon, Spain, Suker, 88.
5. Shoya Tomizawa, Japan, Suter, 82.
125cc
1. Nicolas Terol, Spain, Aprilia, 43 minutes, 49.303 seconds.
2. Pol Espargaro, Spain, Derbi, 44.09.654.
3. Esteve Rabat, Spain, Aprilia, 44.09.858.
4. Jonas Folger, Germany, Aprilia, 44.18.832.
5. Jakub Kornfeil, Czech Republic, Aprilia, 44.19.217.
6. Bradley Smith, Britain, Aprilia, 44:19.289.
7. Marc Marquez, Spain, Derbi, 44.20.708.
8. Jasper Iwema, Netherlands, Aprilia, 44:22.276.
9. Tomoyoshi Koyama, Japan, Aprilia, 44:31.145.
10. Luis Salom, Spain, Aprilia, 44:35.431.
Standings (After 9 of 18 races)
1. Marc Marquez, Spain, Derbi, 166 points.
2. Pol Espargaro, Spain, Derbi, 151.
3. Nicolas Terol, Spain, Aprilia, 143.
4. Bradley Smith, Britain, Aprilia, 115.
5. Tomoyoshi Koyama, Japan, Aprilia, 84.
