Sykes secured his third race success of the season at the Autodromo do Algarve with the Kawasaki Racing Team rider coming through in 31:42.011.
The Brit pipped 2011 world champion Carlos Checa, who was 0.300 off the pace, in what was a tight finish between the front two.
Marco Melandri, meanwhile, was forced to retire after battling with championship rival Max Biaggi and sliding off the circuit at turn 11.
Despite the contact with the stricken Melandri, Biaggi was able to stay upright, the accident serving to break up the pack.
Sylvain Guintoli of France finished in third, over two seconds behind the Spaniard, for PATA Racing Team, with Biaggi of Italy in fourth.
Brett McCormick was fifth with Jonathan Rea in sixth. Loris Baz, Hiroshi Aoyama, Ayrton Badovini and Michel Fabrizio completed the top 10.
Race one results
1. Tom Sykes (Kawasaki Racing Team) Kawasaki ZX-10R 31'42.011
2. Carlos Checa (Althea Racing) Ducati 1098R 31'42.311
3. Sylvain Guintoli (PATA Racing Team) Ducati 1098R 31'44.743
4. Max Biaggi (Aprilia Racing Team) Aprilia RSV4 Factory 31'53.575
5. Brett McCormick (Team Effenbert Liberty Racing) Ducati 1098R 31'53.782
6. Jonathan Rea (Honda World Superbike Team) Honda CBR1000RR 31'53.803
7. Loris Baz (Kawasaki Racing Team) Kawasaki ZX-10R 32'10.704
8. Hiroshi Aoyama (Honda World Superbike Team) Honda CBR1000RR 32'11.592
9. Ayrton Badovini (BMW Motorrad Italia GoldBet) BMW S1000 RR 32'13.518
10. Michel Fabrizio (BMW Motorrad Italia GoldBet) BMW S1000 RR 32'13.598
11. Leon Camier (FIXI Crescent Suzuki) Suzuki GSX-R1000 32'13.721
12. John Hopkins (FIXI Crescent Suzuki) Suzuki GSX-R1000 32'15.178
13. Eugene Laverty (Aprilia Racing Team) Aprilia RSV4 Factory 32'19.854
14. Alexander Lundh (Team Pedercini) Kawasaki ZX-10R 32'20.004
15. Matteo Baiocco (Red Devils Roma) Ducati 1098R 32'21.408
16. Lorenzo Zanetti (PATA Racing Team) Ducati 1098R 32'21.677
17. Norino Brignola (Grillini Progea Superbike Team) BMW S1000 RR 32'24.445
18. Lorenzo Lanzi (Liberty Racing Team Effenbert) Ducati 1098R 32'42.367
19. Leon Haslam (BMW Motorrad Motorsport) BMW S1000 RR 32'21.209
RT. David Salom (Team Pedercini) Kawasaki ZX-10R 27'26.899