The Storm players spoke early in the week about ensuring they delivered a fitting performance in Smith's milestone game.
Scoring seven tries to one at AAMI Park in Melbourne, they did so in spades.
And captain Smith, as usual, was front and centre despite taking a pectoral injury into the game.
The 34-year-old topped his team's tackle count and had four try assists.
"The players really put in a big effort for Cameron," coach Craig Bellamy said.
"He's really put in a whole heap of big efforts in his 350 game career so it was just a bit of payback and they did a great job."
Smith, who joined Canterbury great Terry Lamb on 350 and now has Darren Lockyer's record of 355 in sight by season's end, said the milestone game was extra special.
"Running out was special and I took a moment there before kick-off just to soak up what I was achieving, but it's hard to take in the milestone because my job's to go out and play well today for my teammates and coaches," Smith said.
The victory reaffirmed Melbourne's status as raging title favourites, while the Sea Eagles cling to seventh spot after their second-successive drubbing.
The scoreline was 8-6 with just one minute remaining in the first half before the Storm threw the ball from one sideline to the other, and then Suliasi Vunivalu barrelled across from dummy half.
That try put the winger among some elite company to have scored 38 tries in his first two seasons, alongside South's Alex Johnston, ex-Balmain flyer Larry Corowa, and Dragons' greats Reg Gasnier and Ron Roberts.
The Storm attack then blew Manly away in the second half, with five second-half tries.
Rookie fullback Jahrome Hughes was a shining light but Bellamy was most pleased with his team's defence.
"Manly have scored more tries in the competition than anyone so for us to keep them to six points was a really good effort," Bellamy said.
The only blemish for the Storm is an ankle injury to five-eighth Cameron Munster, which is likely to keep him out of Friday night's clash with North Queensland.
Manly's woes may continue into the week with Addin Fonua-Blake put on report for a high tackle that caught the jaw of Storm halfback Cooper Cronk.
And their next task isn't much easier, taking on second-placed Sydney Roosters.
"We missed too many tackles and made too many fundamental errors and to beat Melbourne we have to be near perfect, and we were far from it," coach Trent Barrett said.
"That's two weeks in a row that we've been really poor and we need to address it and address it in a hurry."
Photo by: ROBERT CIANFLONE/GETTY IMAGES (Cameron Smith of the Storm runs out for his 350th NRL match, against Manly at Melbourne's AAMI Park).