Fallout 2 is notable for being the first video game to feature same-sex marriage through opportunities to marry Miria or Davin, a sister and brother working at the slaughterhouse in Modoc. According to game designer Chris Avellone in 2019, nobody at Black Isle Studios working on the game was against the inclusion of same-sex marriage, and noted that "fans didn't seem to care" about it when playing the game. He believed the reason for this reception was because of it only being offered in Modoc, a tight-knit small town "where things can get wild and weird" that was more receptive to it than a more "modern" location like Vault City.

In the top-left corner of the map to Broken Hills, four metal chests can be seen, but seemingly cannot be easily accessed. In order to reach them, go near the top-right corner of the map and click on the half-hex right between the fence and the part of the grid which you click to enter the world map, and then click the half-hex right above the fence. Your character will then briefly walk off-screen and appear on the other side of the fence, which will allow you to make your way to the chests. These chests contain the stock of all four shops in Broken Hills, which can be stolen from safely without losing Karma or affecting your Reputation.

Ethyl Wright's name seems to be a play on Ethyl Alcohol, the common name for ethanol, also simply known as "drinking alcohol". This fits the fact that her family's livelihood is based around distilling alcohol, and her disapproval of it.

At the game's launch party, "Gecko in a can" promotional items were given out. This was actually a plush gecko in a can, designed to appear as if it was food intended for consumption.
Originally the plan was to have "dog meat in a can", but no suitable dog plush could be found.

Prior to releasing Fallout 2, Black Isle Studios ran a trivia contest both online and through an Australian gaming magazine called PC Powerplay. Lucas Kawarski of Jaktorow, Poland and Cameron Rapmund of Fairfield West, Australia were the two winners of the contest on September 24, 1998 and had two NPCs named after them in the game.

Lucas is found in Arroyo near a giant head statue and Cameron is found at the end of the Temple of Trials.

There is a special encounter in which a player can come across a whale's corpse in the middle of the desert, called "Crashed Whale." The description on the whale itself says "This whale appears to have fallen from a great height", and next to the whale's corpse is a box containing a flower pot of daisies.
This is a reference to the book The Hitchhiker's Guide to the Galaxy, in which a pair of nuclear missiles were transformed mid-air by an Infinite Improbability Drive, turning them into a sperm whale and a bowl of petunias.

Marcus, the Super-Mutant sheriff of Broken Hills, will sometimes shout "I am NOT a merry Mutant!" when he's hit in combat. Marcus is voiced by Michael Dorn, who is best known for playing Worf from Star Trek: The Next Generation, and the phrase comes from the same show, namely the episode Qpid in which "Q" forces the main crew into a recreation of Robin Hood, in which he protests by yelling "I am NOT a merry man!"

It's possible to obtain an item call the "Fallout 2 Hintbook" after completing the game. Using the book will give the player 10,000 experience points, and increase all skills to 300%. It will also raise all stats to 10 and increase HP to 999. It has an unlimited number of uses.

In New Reno, there is a Boxing Arena in which the player can participate in Boxing matches. Two NPCs that the player can fight, Evan Holyfeld and Mike "The Masticator", reference the infamous boxing match between Evander Holyfield and Mike Tyson in which Mike Tyson bit and tore a chunk of Holyfield's ear.

Evan Holyfeld's dialogue alludes to this as well, and if the player fights and loses to Mike "The Masticator", there is a chance the player will be holding a unique item - their own ear, alongside with a permanent -1 to their Charisma stat.

In Golgotha near New Reno, a grave can be found with the words "Tim Cain. Founder, Lover, Fighter, Programmer."

Timothy Cain is the original creator of the Fallout series and setting. He was the lead programmer on Fallout and one of the six people responsible for the game's original design.

The Hubologist faction found in San Francisco are largely a parody of the real-world religion of Scientology. The founder of the Hubologists, Dick Hubbell, is a parody of L. Ron Hubbard, who was the founder of the Scientology religion. There is also two New Reno porn-star Hubologists called Juan Cruz and Vikki Goldman, another parody of the then-outspoken advocates of Scientology and Hollywood actors Tom Cruise and Nicole Kidman.

The "Cheesy Poofs" item is a reference to the cartoon South Park, as Cheesy Poofs are Eric Cartman's favorite snacks in the cartoon.

There are three unused perk/reputation statuses in the game.
"Virgin of the Wastes" is a status that has no actual effect on the gameplay. It can naturally be removed after sleeping with any sex-specific characters. The description for it reads "You really need to get out more. Your sexual exploits have been... well, two dimensional." "Alcohol Addiction" is a status that was to be used for when the player ends up building an addiction to alcohol-related items in the game. It has no coding associated with it, just the art and description. "You have a problem with alcohol. Actually, you have many problems with your drinking habits." "Tragic Addition" is another addiction status that would have occurred after using a pack of Tragic Cards, which is a reference to Magic the Gathering. The effect would stop map travel periodically to say "You feel a burning desire to open another box of Tragic cards."

There are posters on several buildings in the game depicting an angry man screaming with his mouth wide open. This is a picture of Maynard James Keenan, lead singer of the band Tool, and the picture is taken straight out of the insert to their 1994 album Undertow.

The in-game description and model suggest that Bozar was intended to be a Sniper Rifle, rather than an inaccurate, automatic, heavy support weapon with a scope. It's likely that it was either repurposed during development, or mistakenly given the statistics of an automatic weapon and never fixed.

There is a special encounter in which you can encounter a shuttle-craft (USS Torres) that has crashed onto the Earth with three red-shirted men around the craft, all dead from dehydration. On their bodies are "Hypos", which can be used and serve as Super Stimpacks but without the HP-loss side effect.

This is an obvious reference to the Sci-Fi series Star Trek, including the popular trope of "Dead Red Shirts" from the oriignal series in which almost any non-essential character in the show wearing a Red Shirt in an episode was certain to be dead not soon afterwards.

The "USS Torres" may be a reference to one or more people, such as B'Elanna Torres who was a Klingon-Human character from Star Trek : Voyager in 1995-2001, another "Torres" in the first episode of Star Trek : The Next Generation, and finally "Adoni Torres" who worked on Fallout 2 as an Intern Artist.

There is a special encounter in which you come across a stone ring called the "Guardian of Forever."

If you pass through it, you are instantly transported into Vault 13, where you can find good loot, as well as come across a Computer Terminal with a "functioning water chip." You cannot leave this area until you interact with the computer. Doing this will make you accidentally break the Water-Chip giving you 1000 exp and the message "You have broken the water chip... the vault has maybe 100-150 days left of water. This comforts you for some reason."

This is a reference to the Sci-fi series Star Trek, specifically referencing the episode The City on the Edge of Forever. In it, Kirk, Spock and Doctor McCoy are transported into pre-WWII America and cannot return home until history is fixed, with the stone ring acting as a portal into the past.

This also suggests that the player (The Chosen One) is directly responsible for the beginning of the first Fallout game, in which the player (The Vault Dweller) has to go out and look for a new Water Chip to replace the broken one, having only about 100-150 days to do so.

There is a special encounter in which you can find a place called the "Café of Broken Dreams."

The café is actually a copy of "Maltese Falcon" in the Hub from Fallout 1, and the name is likely a reference to "Boulevard of Broken Dreams", a short story written by Harlan Ellison where the main character sees dead people from the past.

Inside the cafe are five Vault character models, three of which talk about what past players did with them in Fallout 1, and two that are unplayable.

Set, Tandi and Dogmeat from Fallout 1 are in here as well. Dogmeat can be recruited if you show him your default Vault suit.

If you hurt Dogmeat, a character named "Mel" with an Australian accent in a leather jacket will appear and attack you. This is a direct reference to actress Mel Gibson who played Mad Max in Mad Max 2: The Road Warrior.

There is a special encounter in which you encounter a man in power-armor that has rusted to the point of immobility. Talking to him makes him ask for "Oil Can", which you can pick up and use on him.

If you help him, he'll thank you by giving you 150 Micro-fusion Cells, then go on his way.

This is a reference to the Tin Man from The Wizard of Oz.

There is a special encounter in which you encounter a Bridge Keeper who will only let you pass after answering three questions correctly. If you answer any of them incorrectly, you die.

This is a reference to the Bridge Keeper scene from "Monty Python and the Holy Grail."