That was over a second up on the existing WSBK lap record at the track, but with the caveat that the layout of the Turn 10 left-hand hairpin has been revised for 2021.
Ducati rider and last year's runner-up Scott Redding led during the morning with a benchmark of 1m41.198s, and that lap stood as the quickest until it was surpassed by Rea on a 1m41.180s with around an hour and 15 minutes left of the day.
GRT Yamaha rider Garrett Gerloff enjoyed a spell at the top of the times when he set a 1m41.147s with an hour to go, before improving to a 1m40.978s and then a 1m40.910s shortly after.
But Rea regained control of the leaderboard when he posted a 1m41.861s and then finally a 1m40.793s to end the first day of 2021 running featuring all five WSBK manufacturers on top.
Honda's Leon Haslam jumped to second inside the final 15 minutes, 0.107s off the pace of Rea and just 10 thousandths up on third-placed Gerloff.
Redding improved to a 1m40.962s late on to wind up fourth on the best of the Ducatis, while BMW's Tom Sykes incredibly made it five different bikes in the top five, 0.472s off the pace.
Toprak Razgatlioglu was sixth for the works Yamaha team ahead of Jonas Folger's satellite MGM Racing BMW - who recovered from a crash in the morning - and the second factory Ducati of Michael Ruben Rinaldi.
Completing the top 10 were Chaz Davies (Go Eleven Ducati) and Andrea Locatelli (Yamaha).
Alex Lowes, who recently recovered from a shoulder injury picked up earlier this year, was 1.173s off the pace of Kawasaki teammate Rea in 12th place, one spot behind Alvaro Bautista on the second Honda, who is recovering from a minor motocross accident.
Michael van der Mark was the slowest of the factory riders in 13th on his BMW, while ex-MotoGP racer Tito Rabat (Barni Ducati) was a low-key 16th.
A total of 20 riders took part in the first day of the test, with Lucas Mahias (Puccetti Kawasaki), Eugene Laverty (RC Squadra BMW) and Loris Cresson (Pedercini Kawasaki) all absent.
Testing continues with an additional eight hours of running on Thursday.