Penrith have kickstarted their premiership defence with an ominous 28-6 thrashing of Manly at Panthers Stadium in the NRL 2022 season opener.

Former Panther Luke Lewis described the performance as "an absolute masterclass" on ABC Grandstand as the reigning Premiers ran in five tries to one in front of 16,901 delighted fans in Penrith.

The victory, in the Panthers' first home game since July, was Penrith's 18th in a row at Panthers Stadium, a run stretching back to 2019.

Manly, who many tipped to be a genuine premiership contender, simply had no answer to Penrith, denied the ball and territory in a lop-sided season opener.

Dally M medallist Tom Trbojevic was kept quiet by some rushing defence as Penrith dominated the ruck and largely kept Manly inside their own half.

Unable to gain ground, Manly could do little to repel the waves of Penrith attacks, with the Panthers' plethora of attacking talent dominating territory to the tune of 76 per cent.

Izack Tago and Stephen Crichton crossed in the first half for the hosts, only to have Manly pull a score back on the stroke of half-time thanks to a tremendous long-range try, finished by Ethan Bullemor.

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Penrith should arguably have been further ahead at the break after Stephen Crichton and, controversially, Brian To'o were denied scores in the opening 10 minutes.

To'o's in particular seemed particularly egregious after Jarome Luai was harshly judged to have impeded Tom Trbojevic, although any direct impact on the Manly man by Luai, as To'o scrabbled, crab-like through the splintered defence, appeared negligible.

Heading into the sheds just a score behind must have given Manly hope for a more competitive second half.

However, the Panthers never let up, with Luai, Apisai Koroisau and Liam Martin all crossing to seal a dominant victory.

Even without star halfback Nathan Cleary — and coming off a 36-0 pre-season thrashing of their own at the hands of Parramatta — the Panthers were able to summon their best.

Cleary's replacement Sean O'Sullivan was excellent, almost scoring one and assisting another, with last year's stars Viliame Kikau and Isaah Yeo also immense.

Manly's Haumole Olakau'atu was placed on report for a late hit and Karl Lawton suffered a bad head knock just before half-time.

This was the Panthers' 18th win in a row at Panthers Stadium, a run that stretches back to 2019 and suggested there will be no premiership hangover for Ivan Cleary's men.