The Donation Machine appears in almost every Shop (and rarely in Black Markets as well as in Arcades or Vaults). Upon touching the Donation Machine, Isaac will donate a coin, causing the displayed coin total to increment. Similar to the Greed Donation Machine, the number of coins donated will persist between runs. Donating money will both upgrade the shop and unlock new items; see below for more information. It will take the player many runs of continuous donations to unlock everything.
Every single donation has a 5% chance to jam the Donation Machine for the current run. When this happens, no more coins can be donated until the next run starts. (Exceptions are covered in the Strategy section below.)
For perspective, this means the player has a 95% chance of being able to donate 2 coins, a 90.3% chance of being able to donate 3 coins, a 51.3% chance of donating 14 coins, a 10% chance of donating 46 coins, and a 1% chance of donating 90 coins. On average, a Donation Machine will accept 14-15 coins before jamming. This equates to an average of 69 runs of maximum donation to reach 999 coins.
An explosion (typically a bomb from Isaac) near the Donation Machine will cause it to randomly drop 2 to 5 coins. These coins will be deducted from the banked total; however, more coins will be deducted than dropped. This can be repeated until donation counter reaches zero, at which point explosions will no longer trigger anything.
Bombing machines will never randomly set the donation counter to 0. This will only occur if there were few coins left in the machine to begin with.
When the number of coins donated increases past 999, the machine will explode, dropping roughly 12 dimes and resetting the total to 0.
Nothing unlocked through donations will be lost if the number of coins in the Donation Machine is reduced in any way. Thus, once something is unlocked, it can never be locked again.
Donation Machines will not appear during seeded runs, challenge runs, or modded runs before Mom has been defeated at least once.
Each donation has a very small chance of giving Isaac +1 luck.
Donating 10 coins to a Donation Machine will increase the chance for an Angel Room to appear for the current floor.
Donation Rewards
Blue Map - Donate 10 Coins to the Donation Machine.
Blue Candle - Donate 900 coins to the Donation Machine.
Stop Watch - Donate 999 Coins to the Donation Machine.
Strategy
Causing the Donation Machine to explode at 1000 cents is not recommended, as it does not unlock anything and removes the ability to trade bombs for coins in future runs until the coin total has been rebuilt back up.
It is recommended to deliberately bomb the Donation Machine such that the banked total is less than 999 cents. This will effectively prevent accidental 1000th cent donations.
With the Error: The given collectible ("Humbling Bundle") does not exist., every cent received from bombing the Donation Machine is doubled; however, the amount deducted from the Donation Machine is mostly less than what is dropped from it. The profit can be used to buy shop items or donate back to the machine until it jams.
With the Placenta, a Blood Bank or IV Bag, and a lot of patience, enough money can be generated to jam the machine.
The Donation Machine can be quickly filled using Azazel and farming coins on the first few floors. When the machine jams, simply reset and farm some more.
The Keeper is good for filling the machine due to starting with Wooden Nickel, Store Key, an extra coin, and a bomb that can give you access to out-of-reach coins or possible coins in vats, corpses, and slot machines. However this is provided that you have the required marks completed and enough skill to avoid dying on the first few floor.
Force Quit Method. This is an easy way to fill up the machine potentially in one run. This method also has no item prerequisite. The game saves the normal and Greed Donation Machine data separately from your main save file; the machine data is only changed and saved AFTER you leave the room. (Does not work on Afterbirth †)
Enter a room with the Donation Machine. Then exit to the start menu normally to save your game.
Continue the game.
Donate money until machine jams or you run out of coins.
Walk out to a different room. Now the game will save the change in coins only.
Force quit the game
Windows: Alt+F4
OS X: Force Quit
Linux: Ctrl+Alt+Esc (may depend on desktop environment)
Consoles: home button and then quit app
Nintendo Switch: eject and reinsert the cartridge
Restart and continue the game. Your save game from the 1st step will be restored. It should look the same as before: Donation Machine is unjammed, but the starting coin count on the Donation Machine is now higher.
Donate money. Walk to different room. Force Quit. Repeat.
Notes: If you accidentally walk by the machine at 999 coins and blow it up by accident, do not leave the room and just Force Quit. The machine will be back at 999.
Despite the 5% jam chance noted above, in actuality, the number of coins it takes to jam a machine is set per floor. Let's say it takes 10 coins to jam the machine. If you Force Quit and try again, it will still take 10 coins to jam the machine even with the higher coin count. When you go to the next floor, let's say it now takes 20 coins to jam the machine. Force quitting on the next floor will still take 20 coins to jam the machine next time. The method works best on a Donation Machine that accepts a large number of coins before jamming.
Error: The given collectible ("Glowing Hour Glass") does not exist. will un-jam the machine and return your coins to you, but the coins you donated will remain in the machine. There are multiple item combinations that allow the player to donate indefinitely:
Buying the Glowing Hourglass from the Shop and donating any remaining coins (re-purchasing the Glowing Hourglass refills its charges).
Using the ? Card will return the ? Card, allowing infinite uses of the Glowing Hourglass.
Purchasing (or otherwise acquiring) a Lil' Battery in the Shop while donating.
Using the Sharp Plug (or the Habit and two bombs) with more than two hearts.
If the Shop has a Lil' Battery for sale, you can donate money, use the Glowing Hourglass to leave the room, re-enter, and charge it with the Lil' Battery endlessly.
Due to exploit potential, the Donation Machine can be very beneficial to fragile characters such as The Lost and Keeper. It may be useful to have a large donation total before starting runs as these characters, since starting a run with an item that grants explosive shots such as Epic Fetus, Ipecac, and Dr. Fetus will allow you to endlessly withdraw coins from the machine until it reaches 0. This can allow game breaking strategies to guarantee success, especially with the Restock and Jera rune. Some of these strategies can be used to spawn Dad's Key as well, eliminating the need for tedious Angel Room farming for keypieces, since the item can open Mega Satan's door.
As of Booster Pack #5, this no longer works, as the Glowing Hourglass now returns donated coins without the donated amount staying in the machine.
Bugs
Bug!
Vita You can donate to the machine if you then leave the room, restart the game and go back to the machine and the amount you donated will still be there and so will the amount of coins you had when entering the level. (This only works if you restart the game by pressing the PS button and then pulling down the paper like icon and not if you press START and exit game.)
Greed Donation Machine, the number of coins donated will persist between runs. Donating money will both upgrade the shop and unlock new items; see below for more information. It will take the player many runs of continuous donations to unlock everything.
modded runs before Mom has been defeated at least once.
Donation Machine.
Bug!
Donation Machine Unlocks 
The Binding of Isaac: Rebirth
