According to the Uno rules and the Uno Attack rules, the Uno reverse card is a card that changes the direction of the game. In other words, the order of turns is reversed.
From the rulebook:

This card reverses the direction of play. Play to the left now passes to the right and vice versa.
If this card is turned up at the beginning of the play, the player to the right now plays first, and play then goes to the right instead of the left.
This card may only be played on a matching color or another reverse card.

The Uno reverse card meme is used as a metaphorical term to describe “the ultimate comeback”. Or to put it in terms of the top definition in the Urban dictionary:

The ultimate comeback that NOBODY can resist. It out powers “no u”. *

*Worth noting is that the Uno reverse card can also be interpreted and used as just a “no u” comeback.

For those of you that don’t remember kindergarten, the “no you” (no u) comeback was, and still is a trendy comeback:

Example:

Your friend: You are mean!
You: No, YOU are mean!

For a long, long time, this was the comeback of comebacks but have now been dethroned.

Example:

Your friend: You are the worst Uno player in the universe!
You: *Pull up and place down the Uno reverse card*
Your friend: *Beaten*
According to knowyourmeme.com , the Uno reverse card meme was defined on April 18th, 2018, as “An upgraded no u” and quickly became popular on Reddit. As of February 2021, the subreddit “UnoReverse” has over 600 members.