The following is a list of unique weapons and how to obtain them:
In the Deathclaw Sanctuary (northwest corner of the world map), follow the caves down and be prepared for many a Deathclaw encounter. In the southeastern corner of the caves is a pool of blood under a column of rock. In this pool there is a heap of gore with the Vengeance, an overpowered Laser Gatling Gun.
After getting access to Little Lamplight, you’ll find a child named “Biwwy” who will sell you the Waser Wifle, an augmented Laser Rifle, for 500 caps. If you have the Child at Heart Perk, you can get it for free (choose “You said you didn’t need it, why not just give it to me for free?”).
Abe Lincoln’s Repeater Rifle
Enter the Museum of Natural History and go to the lower levels. In the Museum Offices, there is a central room with a gun case. Lincoln’s Repeater Rifle is here, a strong Hunting Rifle that uses .44 rounds.
In Girdershade, in the southwest corner of the world map, the town letch, Ronald, has a Sawed-Off Shotgun named the Kneecapper. You’ll have to kill him to get it, passively (via a pissed off radscorpion) or actively (a shot to the head).
In Evergreen Mills, in the southwest corner of the world map, you’ll find a heavily protected raider hideout, including a Super Mutant Behemoth. Inside the center building is a series of caves where the raiders have set up a brothel and a bar. One of these raiders won’t attack you, and his name is Smiling Jack. He’s a trader, but you should trade him a bullet to the head for his Terrible Shotgun, a better Combat Shotgun.
One random event while exploring the capitol wastes is an inexplicable explosion. Head to this area to find the Firelance, a souped-up Alien Blaster and some scattered ammo.
Jack the Ripper
This upgraded Ripper can be found at the lower-middle of the S-shaped map of the Deathclaw Sanctuary. It’s on a dead Enclave Officer in a pile of bodies, next to a giant ant.
Sydney's 10mm "Ultra" SMG
Inside or just the outside Museum of History in Downtown DC you'll find a Super Mutant-fighting Ghoul named Sydney. She asks for help defending the area from Super Mutants. You can help her and if she dies, take her "Ultra" SMG or just kill her and steal it.
A3-21's Plasma Rifle
In the "Replicated Man" sidequest, don't to turn Harkness in to Dr. Zimmer. Instead speak with Harkness and chose to unlock his repressed memories. Once you do this, speak with him again and tell him that he should not kill Dr. Zimmer, but instead tell him to run away. He will thank you and give you his old (albeit more-powerful) Plasma Rifle! You may be able to kill him for it too.
Once you gain access to the Brotherhood Citadel you can take, search or lockpick anything that you want. When you are in the Solar room you can lockpick the Elder Lyons safe (if your lockpick skill is high enough) and find 300 caps, other misc. items and Smugglers End, a powerful laser pistol.
O1' Painless rifle
In the Republic of Dave, in the northeast corner of the world map, kill Dave to get his key and access to his safe. Inside is the Ol' Painless Rifle.
Xuanlong Assault Rifle
This powerful Chinese Assault Rifle is located on the body of Jiggs in the diner ner the Jury Street Metro Station. This location can be discovered via the Museum of Technology mini quest, Jiggs' Loot.
This is dropped by the Drifter in Dickerson Tabernacle Chapel (upper west of world map). It is an augmented sniper rifle.
This augmented Sniper Rifle is in a Very Hard locker in the Sniper Shack to the west of Rockbreaker's Last Gas (Middle west of worldmap).
The Mechanist has this augmented laser pistol. Get it by giving him the Antagonizer's costume. Note: this results in negative Karma.
This powerful missile launcher also is 5 WG less in weight than its normal counterpart. Find it in the storage room in the lower level of Fort Independence.
Zhu-Rong v418 Chinese Pistol
Found in the east wing of L.O.B. Enterprises in a Very Hard Locked case on a desk upstairs, the Zhu-Rong is a pistol that will ignite flammable substances.
The augmented Scoped .44 Magnum can be obtained from Agatha after completing both Agatha's song and an additional Sheet Music fetch quest (in the Springvale school). You must request a reward from here in the dialog tree for this.
In the very bottom of Falls Church/Mason St. Metro you will find a radiated ghoul camp; here you will find the Burnmaster, an improved Flamer.
Stabhappy is an upgraded Combat Knife in the "Raid Shack", a house of Raiders. Just head directly East from the Bethesda Ruins and you will see a fenced in house called the Raid Shack. Kill the Raiders inside and one of them carries Stabhappy!
In the MDPL-13 power station, enter the door on the right. You will be in an office and on the table in the center of the room is Fisto! the upgrade to the Power Glove. Beware of Ghouls.
Fawkes Super Sledge
When you first meet Fawkes after freeing him from the locked door, talk to him and trade equipment with him. He will already have an item called the Fawkes Super Sledge in his inventory which you can take from him.
The Break is a unique pool cue which can be found laying on top of the pool table outside of "Eulogy's Crib" in the middle of Paradise Falls.
Board Of Education
The Board Of Education is a unique nail board located in one of the abandoned shacks in the "Clifftop Shacks" area just outside of the Oasis. It is laying next to a skeleton lying on one of the beds.
Junders' Valid Points
Junders' Valid Points are a set of unique spiked knuckles. They can be obtained from the body of Junders Plunkett after you kill him. his hideout is located inside Arlington Cemetery and is on the top of a hill. (Note: if you have enough good karma and have the note stating he is a wanted man, his dead body will also contain his finger which can be redeemed for a nice 1000 cap reward. If you don't have the note is can be found on the body of a dead Regulator on the steps of the nearby metro station).
Slightly more powerful switchblade, can be gotten from Butch after the Trouble at the Home Front quest. Kill him or ask him to follow you.
This sword is locked in a hard locked cabinet named "sword cabinet" in Vance's room upstairs in Meresti Station.
Found in the flooded metro, the Shocker is a more powerful power fist (24 damage if 100% repaired).
Occam's Razor is an augmented combat knife found on the CO in the very bottom of Ft. Bannister.
Eugene is an improved Minigun which can be given to you by your choice after completing the side quest Reilly's Rangers. Reilly rewards you for helping them you have a choice between Eugene and armor.
In the slaver camp of paradise falls (you may have to go there in the main quest), on a pool table outside in the main are (outside the shops Eulogy Jones' pad and the slave cages)there will be an augmented version of the pool cue. Beware of slavers, people with good karma.
In Canterbury Commons, located in the far middle east part of the world map, you will find a Tire Iron called the Highwayman's Friend. The weapon is on a shelf in the back room of Dominic and Machete's house.
In Evergreen Mills (NE of Girdershade) There you will discover a raider hangout including full bar and brothel. A fellow named Smiling Jack resides here and will not shoot you. Kill him for the Terrible Shotgun, a souped up Combat Shotgun.
This gun is a unique variation of The Fat Man that shoots 8 mini nukes at once. It is the most powerful weapon in the game and can be found on a table in a secret room in the armory of the National Guard Depot. There is a computer that asks for a 4 digit passcode. The passcode can only be found by piecing together the Keller Family Holotapes. It comes with 5 mini nukes.
This high powered Sniper Rifle can only be found in The Pitt add-on. In the Arena, beat the final challenger and search his body for the Infiltrator.
Obtained from the body of a dead alien lying a few feet away from his crashed spaceship. The alien crash site is found north of MDPL-13 Power Station and northwest of the Greener Pastures Disposal Site. It has unique ammo as well, the Alien Power Cell, which is incredibly rare. The chance of a critical strike with this gun is nearly 100%. It can be repaired with the Firelance, but degrades rapidly. Its damage is 100.
Colonel Autumn's Laser pistol
This gun is a modified, fully automatic version of the standard laser pistol with a rate of fire comparable to the Gatling laser. It has a 30 round magazine, uses minimal action points, and is repaired with the common laser pistol. The weapon does 75 damage while using the same Energy Cell ammo as a standard pistol. This version is also lighter than a standard laser pistol, with a weight of 2. This unique pistol is considered a quest item and cannot be dropped. The only way it can be removed is by using it as spare parts to repair a regular laser pistol, but this will destroy it permanently. Also, since it is a quest item, the weapon can only be repaired manually. It is located from Citadel to the Jefferson Memorial's rotunda.
The guard at the front entrance of Paradise Falls has it. He will give it to you if you ask him if he needs help.
Colonel Autumn's 10mm Pistol
This is a unique pistol that does double the damage of the standard variety. It can be repaired using standard 10mm pistols and is obtained from Colonel Autumn's body at 100% condition the Jefferson Memorial rotunda during the "Waters Of Life" quest.
The first part of the schematic for the Dart Gun is at the MDPL-05 Power Station, on the northwest tip of the Capital Wasteland. Another part is obtained from Hannibal Hamlin after completing the Lincoln Memorial quest for the slaves. The last schematic is located in a locked chest at the Boutique Le Chic in Tenpenny Tower. Parts required are as follows: a toy car, surgical tubing, paint gun, and Radscorpion poison gland. The Dart Gun cripples your target's legs and thus is very useful when used on fast melee opponents such as Deathclaws. It also poisons your target for eight seconds.
This is a schematic weapon built from the following: a motorcycle gas tank, motorcycle handbrake, lawnmower blade, and pilot light. One of its schematics is found with Vance, who gives one to you after the Blood Ties quest. Lucky Harith, the wandering merchant, has another. There is a final set near a workbench in a Red Brotherhood Outcast shack, to the southwest of SatCom Array NN-03d. The shack does not appear on the map, but is at the base of the hill the array is built on. Every schematic obtained increases the condition of the weapon when it is built. Its damage is 40 plus 10 fire damage over five seconds.
This is a unique sledgehammer found at the Anchorage War Memorial, inside the storage room with the broken door. It can be repaired with sledgehammers. The Tenderizer damages enemy armor on each hit by 5 points and is the only "enchanted" weapon.