The start of the session was delayed on Saturday morning as fog descended at Jerez.
But the gloom didn't lift for Marco Melandri - buoyed after starting on pole - who was leading when the Italian rider was forced to retire with four laps remaining due to a technical issue.
Melandri fastest in final practice in Spain
Rea took advantage of Melandri's misfortune to hold off Chaz Davies and Tom Sykes in claiming victory.
It is Rea's 13th World Superbike win of the season, and the first time he has enjoyed success at the Spanish venue.
Chaz Davies: 'Perfect end to a disastrous weekend'
Thrilling finish as Davies pips Rea in Aragon