If you didn't play civ 5 then you ultimately have a double transition - a lot of the differences between 4 and 6 were present in 5.
But Civ6 isn't really that complex, it's still the same civ game, even though visually it looks very different from 4.
(edit: I forgot to include a couple civ5 things)
Things added in Civ5 that are in civ6
Hex Tiles
Why have 4 edges when you can have 6?! Honestly besides being able to move differently, this is just a visual thing.
1 Unit per Tile
Perhaps the most impactful change from 4->5, the idea was to finally get rid of the "doomstacks" of past civs and mechanics like collateral damage.
Combat
The combat did simultaneously change to an HP based system instead of the "two unit enter, one unit leaves" of stacks. Its important to note that part of this is that an empire generally has fewer units fielded than before, and units are more durable than before to reflect that.
Ranged Units
While civ4 had some ranged bombardment capability, it mostly focused on first strikes and defender vs attacker bonuses. Now, some units like archers can indirectly attack another tile, and won't take damage from doing so, and importantly, this can kill units. Cities themselves have a ranged attack, and unlike civ4 have inherent defensive ability, so you don't need to garrison them all constantly.
Trade Routes:
Rather than the commerce generating system in civ4, trade routes are discrete trader units moving around on the map. They can generate gold for you if sent to foreign cities, or they can make food and production if sent domestically.
Tourism & Great Works
This was a big change, but one that can be ignored for the most part as a new player. The idea that one can generate great people to create these items isn't that crazy - after all,
Religion
Just like civ4, great prophets can found religions. But the system was greatly deepened and expanded. First, the "Faith" resource was added as religious currency. Second, religions are now very customized instead of all being carbon copies like civ4. (To quote the civ4 game manual on that topic, "we're game designers, not theologians.") All civs can have their own pantheon, effectively a small bonus that usually relates to nearby terrain or resources. Civs earning a Great Prophet can found a religion, which itself has beliefs the player can choose, including a "founder" belief that only effects the creator, and follower beliefs that affect any city with the religion. As usual, religion is spread by missionaries.
Buy most things with Gold
No longer restricted to just Universal Suffrage, in civ5 the commerce yield has been removed and now science and gold are independently generated. With gold still being used to pay for things in your empire, having a surplus can now be used to instantly purchase a unit or building.
Strategic Resources
Strategic resources now accumulate per turn based on how many sources you have of them. They are consumed by military units and some buildings. Instead of being able to build unlimited tanks if you had access like civ4, now you need 1 unit of oil to fuel 1 tank. Fairly logical, although it does mean you have to watch the map a little.
Global Happiness
Instead of happiness and health per city, happiness is in some part a global number that represents the net of your citizens consumption vs the luxury resources and entertainment you provide them.
Unique Civ bonuses
Instead of having leader traits, civs have unique abilities in addition to their unique unit and building. This is a different approach to civ design that most people feel has made the game more re-playable.
City States
City States are minor, one city entities that major civs can interact with for various benefits. Namely, "CS" are divided into a few groups like cultural, mercantile, maritime, etc, each providing an economic benefit for good relations. You can capture them, but there may be diplomatic consequences!
Further things civ6 added
Units
Workers used to build a farm or mine every few turns. Now they can build instantly, but only have a limited number of charges. They still do the same thing, though- improve your tiles.
Military units are the same as always, although they changed combat from being a ratio of strengths to a difference of strengths. So instead of seeing +25% damage, you'll see +5 strength. Any time two units differ by X points of strength, the outcome is the same no matter if they are 20 vs 25 or 100 vs 105. Furthermore, military units can eventually merge to become more powerful. Two copies of a unique - like a pikeman- can merge to become a Pikeman Corps, while 3 can form a Pikeman Army. This helps players with a big military concentrate power into one spot.
Civics Tree & Policy Cards
Representing a civilization's societal and cultural growth has always been hard. In civ4, you unlocked civics over time to help form a government. In civ5, you put culture into "social policy" trees which were fixed, but had more choices. In civ6, the tech tree has been split so that things like gunpowder and radio are science based technologies and cultural things like feudalism and now culture based "civics." It's a second tech tree that uses culture instead of science.
To represent your government, the player now has policy cards that they can choose to slot. This system is a hybrid of civ4 and civ5 - there are many options, but you can change them relatively freely. As you progress, there are increasingly advanced tiers of government that allow you to slot more policy cards at once.
Even more unique civs
Building on civ5's development, every civilization has a unique ability, and each leader has a unique ability too. Some civs have more than one leader, and Eleanor of Aquitane is a leader who can be used in two different civs!
In general, the civs are even more differentiated than they were before.
City states also gained unique bonuses they grant to whoever has the best relationship with them. For example, zanzibar grants copies of unique luxury resources.
Wonders on Tiles
Wonders are now built on tiles themselves. Cities still build them, but you must have a valid place to put them - pyramids in the desert, for example.
Districts
The crown jewel of civ6, districts are essentially extending the idea of putting wonders on map tile to city buildings. We have always had city buildings that group naturally: The barracks, armory, and military academy; the monument, theater, and broadcast tower; the workshop, factory, and power plant. What districts do is essentially take those groupings of buildings and give them a special tile to build them in. So instead of building your workshop and factory in the city center, a city will build an industrial zone, and then the workshop will be built there. But why do this? Well...
Adjacencies
Part of the recurring theme of tying more things to the map is the idea of Adjacency Bonuses. Both Districts and Improvements can have them. For example, where civ4 has farms getting more food from irrigation and eventually universally at biology, in civ6 farms get bonus food for being near other farms at various points in the game. As an example, a late game, fully mechanized farm farm will get +1 food for each farm next to it. If you build a triangle of 3 farms, then each farm would give +1 food by itself, and +2 food for being next to two farms, for a total of +3 food each.
Districts really flesh out the system. Most districts you might associate with a yield - science, culture, faith, gold, production- have adjacency bonuses. For example, a Commercial Hub (where you put banks and markets) gets extra gold if it's next to a river or harbor. A campus (where you put libraries and universities) gets extra science for being near mountains. Often, a good district location provides a bigger bonus than many of its buildings! This gameplay feature creates a sort of city planning puzzle that can feel daunting at first, but is easy to become proficient in.
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And that's about 15 years of civ development. Yes, there are other systems like governors and loyalty, and natural disasters, but the core gameplay differences is captured above. It's really not that different - you still build cities, improve tiles, and train units. And you still put your neighbors head on a spike when needed.