Sainz set the pace courtesy of his 1m28.942s effort in the first representative dry running of the weekend to sit pretty by a little over a tenth ahead of Hamilton and Norris.
Meanwhile, defending champion Max Verstappen ran fourth quickest to pip his Ferrari title rival Charles Leclerc.
After the changeable conditions of the first practice session left only 10 drivers to set a time, the track was a hive of early activity as soon as the hour-long FP2 got underway on Friday.
Sainz had been the first driver to head out on track, the Ferrari shod in medium-compound C2 Pirellis, and was soon followed by Sebastian Vettel and Norris on the harder C1 rubber.
With all 20 drivers venturing onto the circuit within the first 90s, the benchmark laptimes kept coming as Sainz, then Valtteri Bottas and Yuki Tsunoda took it in turns to set the pace.
The downside of the congestion, as Max Verstappen slowed out of Stowe to complete a systems check, was a fight for track position – George Russell was notably delayed by Tsunoda through Luffield.
The Alpines and Williams duos emerged straight away on the C3 soft tyres, which allowed Esteban Ocon to temporarily occupy first place courtesy of a 1m33.081s lap after four minutes.
He was then surpassed by teammate Fernando Alonso, the two-time champion running 0.015s quicker until Vettel moved top by 1.6s aboard the updated Aston Martin AMR22.
It was after five minutes that the Ferrari and Red Bull usual suspects rose to the fore.
Leclerc lowered the benchmark to 1m30.784s to pip Sainz by 0.014s and in turn found sixth tenths over Verstappen.
Sainz backed off for a cool lap and then pushed again to set a new yardstick on the medium tyres, his 1m29.962s moving him eight tenths clear of Scuderia teammate Leclerc.
Hamilton moved third on the same yellow-walled compound despite lingering complaints over the Mercedes W13 bouncing excessively at higher speed.
Verstappen then did enough to split the Ferraris after 11 minutes before Leclerc improved once more to sit top with a 1m29.639s to head Sainz, Verstappen and Sergio Perez.
Verstappen sure enough improved again to divide the red cars, his 1m29.885s moving him within three tenths of Leclerc.
In a frenetic opening third of FP2, Leclerc then lowered the times to 1m29.462s on mediums to end the yellow-walled running as the pacesetter with a tenth in hand over Sainz.
A lull while all 20 cars hit the pits then gave way to the fastest soft-tyre running, with Norris soon climbing to…
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