The Briton took victory in Brno in the Czech Republic, after holding off Yamaha team-mate Michael van der Mark, a double race winner in Donington, to win by just over a second.
Chaz Davies completed the podium after Rea clinched the overall wins record with his 60th victory in Race 1 on Saturday.
Haslam, Lowes involved in early crash as Race 2 red-flagged
19/09/2021 AT 21:55
Rea crashed after he collided with Kawasaki colleague Tom Sykes.
Rea was only on his third lap when the touch between the two bikes occurred.
Fourth place was taken by Eugene Laverty, like Rea, from Northern Ireland.
Lowes spoke after the race to give thanks to those who had helped him:
"I am really happy - thanks to everyone who got me here..
"I was consistent and tried to be as smooth as I could."
1. JONATHAN REA - 270 - KAWASAKI
2. CHAZ DAVIES -189 - DUCATI
3. TOM SYKES - 179 - KAWASAKI
'He's done it, finally!' - Lowes takes his first World Superbikes win
4. MICHAEL VAN DER MARK - 176 - YAMAHA
5. MARCO MELANDRI - 156 - DUCATI
6. ALEX LOWES - 129 - YAMAHA
7. XAVI FORES - 126 - DUCATI
'I'll keep it short... before I start crying!' - Lowes reacted to first win
8. TOPRAK RAZGATLIOGLU - 84 - KAWASAKI
9. LORIS BAZ - 67 - BMW
10. JORDI TORRES - 64 - MV AGUSTA
11. LEON CAMIER - 63 - HONDA
12. LORENZO SAVADORI - 62 - APRILIA
13. EUGENE LAVERTY - 47 - APRILIA
14. MICHAEL RUBEN RINALDI - 44 - DUCATI
15. LEANDRO MERCADO - 42 - KAWASAKI
16. ROMÁN RAMOS - 35 - KAWASAKI
17. JAKE GAGNE - 20 - HONDA
18. PJ JACOBSEN - 18 - HONDA
19. YONNY HERNANDEZ - 16 - KAWASAKI
20. LEON HASLAM - 14 - KAWASAKI
21. DAVIDE GIUGLIANO - 11 - APRILIA
22. BRADLEY RAY - 3 - SUZUKI
23. LUKE MOSSEY - 2 - KAWASAKI
24. ONDREJ JEZEK - 2 - YAMAHA
Tom Sykes hospitalised after heavy crash in Catalunya, suffers concussion but nothing else
19/09/2021 AT 21:20
Rinaldi wins Race 2 in Catalunya as Toprak retakes championship lead
19/09/2021 AT 15:28