Riding in his 100th grand prix and starting on pole for the fourth race in a row, Honda rider Marquez briefly surrendered first place to Italian Yamaha pilot Valentino Rossi on the opening lap at the sun-drenched Andalusian circuit.
The 21-year-old immediately seized back the initiative from his boyhood hero, however, and opened up a gap of around five seconds at the front before easing off in the final stages and coasting over the line to delight his home supporters.
It was his first victory at Jerez and he is the first rider to win the opening four premier class races of the year since Mick Doohan in 1992.
Rossi held off a late challenge from Marquez's team mate Dani Pedrosa to secure second place and another Spaniard, Jorge Lorenzo of Yamaha, came in fourth to mark a disappointing 27th birthday for the former champion in his 200th grand prix.
"I was expecting more of a bunched-up race but I saw that I started with a good rhythm and I was feeling in good shape," Marquez told reporters.
"Without pushing too hard I saw that I was pulling away and decided to keep pushing it because I didn't know what was going to happen in the final stages," he added. "I am very pleased to win here in front of all the fans."
After four of 18 races, Marquez, who became the youngest premier class world champion last season, tops the standings on a perfect 100 points. Pedrosa is second on 72 points and Rossi third on 61.
In the Moto2 class, Mika Kallio of Finland came in first ahead of Swiss Dominique Aegerter in second and Jonas Folger of Germany in third.
Italian Romano Fenati won the Moto3 race with Efren Vazquez second and fellow Spaniard Alex Rins third.
Riders and teams next head to Le Mans for the French grand prix in two weeks.
1. Marc Marquez (Spain) Honda 45:24.134
2. Valentino Rossi (Italy) Yamaha 45:25.565
3. Dani Pedrosa (Spain) Honda 45:25.663
4. Jorge Lorenzo (Spain) Yamaha 45:32.675
5. Andrea Dovizioso (Italy) Ducati 45:51.628
6. Alvaro Bautista (Spain) Honda 45:51.740
7. Aleix Espargaro (Spain) Yamaha 45:52.051
8. Bradley Smith (Britain) Yamaha 45:52.081
9. Pol Espargaro (Spain) Yamaha 45:53.553
10. Stefan Bradl (Germany) Honda 45:57.006
11. Nicky Hayden (U.S.) Honda 45:59.624
12. Hiroshi Aoyama (Japan) Honda 46:04.217
13. Scott Redding (Britain) Honda 46:07.964
14. Yonny Hernandez (Colombia) Ducati 46:16.429
15. Hector Barbera (Spain) Avintia 46:19.007
1. Marc Marquez (Spain) Honda 100
2. Dani Pedrosa (Spain) Honda 72
3. Valentino Rossi (Italy) Yamaha 61
4. Andrea Dovizioso (Italy) Ducati 45
5. Jorge Lorenzo (Spain) Yamaha 35
6. Stefan Bradl (Germany) Honda 30
7. Aleix Espargaro (Spain) Yamaha 30
8. Bradley Smith (Britain) Yamaha 28
9. Andrea Iannone (Italy) Ducati 25
10. Pol Espargaro (Spain) Yamaha 25
11. Nicky Hayden (U.S.) Honda 23
12. Hiroshi Aoyama (Japan) Honda 19
13. Scott Redding (Britain) Honda 14
14. Yonny Hernandez (Colombia) Ducati 13
15. Alvaro Bautista (Spain) Honda 10
- Sports & Recreation
- Valentino Rossi
- Dani Pedrosa
- Jorge Lorenzo