Later, in "Payback", it is used by the VC Bookie in a game of Russian roulette between Mason and Woods. After the gun fails to fire on Woods, Mason, gambling the next shot is in the gun, uses it against one of his captors and kills him. The gun is unusable for the rest of the mission, probably since there was only one round put in it, so the Bookie's CZ75 is kept.
The Python is unlocked at level 18. It has the highest maximum and minimum damage of all the handguns in multiplayer, making it a highly effective secondary. The Python also has the highest hipfire accuracy of any other weapon in the game. It is able to kill in two shots at close range and four shots at long range. In Hardcore modes, it is by far the most effective handgun, as it is a one shot kill at any range. The main disadvantages of this weapon are the low six round capacity, high visual recoil, and a long reload time without a Speed Reloader, Dual Wield and/or Sleight of Hand.
The Dual Wield attachment is very effective, especially in close quarter combat as it can kill with a single shot combination (one shot from each Python). Dual Wield Pythons also receive Speed Reloaders for free as well, meaning all six shots are reloaded at once. The main downside to the Dual Wield attachment on the Python is the that the weapon will have a much slower switch time, which can mean death when needing switch weapons in the middle of combat. The ACOG Scope for the Python is also useful, helping to control its high visual recoil and improving its long range usefulness, making it an ideal secondary for use with shotguns and SMGs.
The Python is a one-hit kill from round 1-10. After that it becomes a two hit kill to the chest, but remains capable of one shot kills, provided they are headshots. It is often not favored in Zombies, due to its low capacity and slow reload. It can, however, be a powerful secondary to use in a pinch.
When the Python is put inside the Pack-a-Punch Machine, it becomes the "Cobra," which gives it 12 shots per cylinder with 96 extra rounds and the Speed Reloader attachment. The damage up-close doesn't increase but its damage at range does which may occasionally be useful at long range engagements.
The Python returns in Call of Duty: Black Ops II in Zombies mode and briefly in the Campaign (only seen holstered and carried by Jonas Savimbi and several Batallón Dignidad fighters). It is exactly the same as its Black Ops counterpart, being able to get one-shot kills up until round 9 and is a good backup weapon to use if in a pinch. Its downsides are it holds six rounds which can run out fast if fired quickly and the fact that it reloads one round at a time. Its upgraded counterpart, the Cobra, also functions the same as its Black Ops counterpart. It doubles magazine size, is a one hit kill until round 16, and adds a Speed Reloader, making reloads significantly quicker.
The Python is the cheapest weapon in Call of Duty: Black Ops multiplayer, tied with the Ballistic Knife and CZ75, costing only 1500, as opposed to all other weapons which cost 2000.
Pack-A-Punching the Python removes the tritium on the iron sights, much like how it was early in development.
The Python seems to be Mason's sidearm of choice, as he uses it in most of his missions.
The Python is capable of gibbing enemies, making it the only pistol that can gib in the campaign.
In early stages of development, the Python was called .357 Magnum.
There is a fingerprint on the top of the Python's barrel.
Castro is seen with a Python in the loading screen of "Five".
The Python was originally supposed to have black iron sights with an Upgraded Iron Sights Attachment, but the hour-long interview showing Gun Game with "Python Speed Reloader" showed the newer white sights as default.
The Python is the only handgun able to support the ACOG Scope attachment in the entire Call of Duty series. It is also the first time in the Call of Duty series that a secondary weapon can be equipped with an ACOG Scope.
The ACOG Scope increases the range of the Python, unlike on any other weapon in the Call of Duty series.
The Python has three different reload animations. The first animation shared by both the Regular and Snub Nose version, the second animation is used when the ACOG Scope is equipped where the cylinder is closed by flicking the wrist (this is due to the ACOG blocking the player models hand), and the third animation is used by the Speed Reloader where all rounds are put in at the same time instead of individually.
In Zombies, the Pack-a-Punched Python is called the "Cobra". Both names are a play on words, as both weapons are named after types of snakes, and a reference to another revolver also made by Colt.
Oddly, when heard from third person, the Python w/ Speed Reloader's reload sound and animation are identical to that of the M1911. This is because all the pistols in Call of Duty: Black Ops use the same third person reload sounds.
Originally, the Python in Gun Game was to have a Snub Nose and Speed Reloader, rather than just a Speed Reloader. This can be seen in early Gun Game videos.
In the Wii version of Call of Duty: Black Ops, it is held with one hand, along with the other pistols.
While reloading without a Speed Reloader, one can see up to three empty slots for the bullets, even if the player is just putting one or two cartridges into the revolver.
Pythons with snub noses appear in the opening cutscene for Mob of the Dead. The Pythons here also have the firing sound of the Five-Seven, and for whatever reason, fire more shots than they actually can hold, as the four characters do not reload them on screen.