The Reds entered the weekend occupying first place in the Premier League standings, with the reigning champions one spot beneath them after six rounds of fixtures.
Writing in his column in the official matchday programme, Henderson detailed his immense respect for Pep Guardiola's side, having battled intensely with them for honours in recent seasons.
The captain said: "There's no doubt that today's game is our biggest of the season so far. The Premier League table tells us this, recent history and the aims of the two clubs tells us this.
"As an opponent, Manchester City are as strong as they come and we welcome them to Anfield in the knowledge that having got a great result at Chelsea last weekend they will be looking for another one today.
"City's record under Pep Guardiola speaks for itself. From a Liverpool perspective, they set the standards that we had to live up to before we could become champions and any team which wants to win the league this season will know that their chances of doing so will be maximised if they finish above City.
"They are the reigning champions and someone will have to take their crown because City won't be handing it over.
"There is a lot of talk about the rivalry between our two clubs, but for the most part this is built on respect and competition. You can't slug it out as we have in recent seasons and not have a rivalry, that wouldn't make sense.
"But by the same token, if you go toe-to-toe with a team like City it would be ridiculous if you didn't recognise their quality and respect them for it.
"Yes, there will be headlines, stories and flashpoints because all of this is part and parcel of elite sport in which one team is vying with another, but I can guarantee that when the game kicks off at 4.30pm today the overriding factor will be respect.
"It is only by having this kind of approach that you give yourself the best possible chance of being successful on the day. If you don't know how good the opposition are and respect that, how can you possibly beat them?
"The mad thing is it's only a couple of games ago that reactionary questions were being asked of City after a home draw against Southampton. Honestly, that baffles me. This Man City are without question one of the most consistently successful teams of the modern era.
"But it is the world we live in now I suppose. A result and performance in isolation is analysed to death, ignoring wider context.
"The flip-side to that sort of reaction is it speaks volumes about the standards being set. It was similar for us last weekend when we drew at Brentford. Was it the perfect result? No.
"Did we want a better one? Of course. But the reality is that every team will play games throughout the season when points will be dropped against opponents whom you're supposedly favourites to beat, because that is just what the Premier League is like.
"We will not take anything away from Brentford. Their effort, desire, commitment and quality was evident throughout the game and the plaudits that followed were deserved.
"At the same time, though, we knew that collectively we had not delivered the kind of overall performance that is required more often than not if you want to thrive in this league.
"There were positives. We scored three good goals, created other chances and generally played pretty well, but this was undermined by individual and collective shortcomings at key moments and this cost us two points.
"This is why it was so important that we responded in the manner that we did against Porto in midweek. It is one thing to have an off-day, it is another thing to allow it to turn into two or three.
"So we will take the knowledge of what we have been doing well and what we've been doing not so well into this fixture. It's up to us to use this knowledge to be the very best that we can be. Nothing else will do today. If we don't set the standards, City will do it for us."