Kawasaki's Sykes delighted the home fans, who had earlier been drenched by a downpour, as track conditions improved throughout the session.
Sykes posted a time of 2mins 06.115secs, three hundreths quicker than Checa on his Althea Ducati.
Guintoli, on his return to WSBK action following his split from Effenbert Liberty Ducati, secured third with an impressive ride.
But it was a day to forget for championship leader Biaggi who could only manage 17th on a rare off day.
Rea too had problems finding pace and both riders now face missing Superpole if they do not find dramatic improvements in Saturday morning's second qualifying session.
1. Tom Sykes GBR Kawasaki Racing ZX-10R 2m 06.115s
2. Carlos Checa ESP Althea Ducati 1098R 2m 06.148s
3. Sylvain Guintoli FRA PATA Ducati 1098R 2m 06.576s
4. Leon Camier GBR FIXI Crescent Suzuki GSX-R1000 2m 06.617s
5. Chaz Davies GBR ParkinGO MTC Aprilia RSV-4 2m 06.684s
6. Jakub Smrz CZE Liberty Effenbert Ducati 1098R 2m 06.795s
7. Eugene Laverty IRL Aprilia Racing RSV-4 2m 06.851s
8. Lorenzo Zanetti ITA PATA Ducati 1098R 2m 06.869s
9. Maxime Berger FRA Effenbert Liberty Ducati 1098R 2m 06.967s
10. John Hopkins USA FIXI Crescent Suzuki GSX-R1000 2m 07.007s
11. Ayrton Badovini ITA BMW Italia Goldbet S1000RR 2m 07.089s
12. Marco Melandri ITA BMW Motorrad S1000RR 2m 07.244s
13. Leon Haslam GBR BMW Motorrad S1000RR 2m 07.401s
14. Niccolo Canepa ITA Red Devils Ducati 1098R 2m 07.404s
15. Loris Baz FRA Kawasaki Racing ZX-10R 2m 07.499s
16. Michel Fabrizio ITA BMW Italia Goldbet S1000RR 2m 07.658s
17. Max Biaggi ITA Aprilia Racing RSV-4 2m 07.723s
18. Jonathan Rea GBR Honda WSBK CBR1000RR 2m 07.740s
19. Davide Giugliano ITA Althea Ducati 1098R 2m 07.810s
20. Hiroshi Aoyama JPN Honda WSBK CBR1000RR 2m 07.996s
21. David Salom ESP Pedercini Kawasaki ZX-10R 2m 09.438s
22. David Johnson AUS Pedercini Kawasaki ZX-10R 2m 10.043s
23. Norino Brignola ITA Grillini Progea BMW S1000RR 2m 11.645s
24. Brett McCormick CAN Effenbert Liberty Ducati 1098R 2m 13.730s