While held, passively modifies Isaac's stats and the way he fires his tears based on the item's current "tune", indicated by the color of the music note.
On use, resets Isaac's tear delay, and cycles between one of three different tunes in the following order:
Isaac's tears are fired in a barrage of up to 10 tears. After all 10 tears are unleashed, or when Isaac stops shooting, a delay equal to roughly 15× Isaac's current Tear Delay (or ~7% of his Fire Rate) is applied before Isaac can start another barrage.
Notes
While in an uncleared room, Angelic Lyre gains a delay between switching modes. In cleared rooms, switching modes can be done instantaneously.
The only way to remove the passive stat modifiers from Angelic Lyre is to drop it, by either replacing it for another active item or through other means that can cause the item to be dropped or removed, such as Butter!
The 3 different tunes are, in actuality, 3 separate items listed in the code, all with the same name and description. Only the Blue variant can be found in the item pools and encountered normally.
As Angelic Lyre can reset Isaac's tear delay when switching tunes, it may be ideal to switch tunes after firing a shot in its Red tune, or after the barrage cooldown of the Yellow tune so that Isaac can continue firing tears without waiting.
Brimstone / Mom's Knife / Epic Fetus / Tech X: Multishot effect granted by Angelic Lyre's Blue and Red tunes, as well as barrage-activated delay of the Yellow tune will not be able to apply to these tear replacements. Stat changes and basic tear effects granted by Angelic Lyre's tunes will still apply.
Technology: Multishot granted by Angelic Lyre's Blue and Red tunes will not apply; Yellow tune's barrage and cooldown will work, however.
Dr. Fetus: Angelic Lyre's tear modifier properties for each tune will apply to Dr. Fetus's bombs, including the multishot and barrage properties.
Void: Once absorbed, Angelic Lyre's tear modifiers won't apply until Void is used again. The tune will change each time Void is used.
Spindown Dice: Using Spindown Dice on Angelic Lyre will reroll it into Rat Poison, which can then be rerolled into Horncob, both of which are rare items.
Only Angelic Lyre in its Blue tune can be spun down into, and the Red and Yellow Angelic Lyres cannot be found with Spindown Dice.
Book of Virtues: Spawns a Blue, Red or Yellow music note wisp when Angelic Lyre is used, based on the tune. When a new wisp is spawned, any wisp spawned from the previous tune will be destroyed. There is no difference in behavior between any of the music note wisps.
Abyss: Spawns 3 Abyss Locusts that each look like blue, red and yellow music notes. The blue locust deals 1/3× damage and moves at default speed, the red locust deals 1× damage and moves at 25% speed, and the yellow locust deals 1/8× damage and moves at 200% speed.
Video Showcase
Gallery
Musical notes that can appear when Angelic Lyre switches tunes.
Butter!
Car Battery / 
Eternal Car Battery: No effect, won't change the order of which the tunes are played.
Brimstone / 
Mom's Knife / 
Epic Fetus / 
Tech X: Multishot effect granted by Angelic Lyre's Blue and Red tunes, as well as barrage-activated delay of the Yellow tune will not be able to apply to these tear replacements. Stat changes and basic tear effects granted by Angelic Lyre's tunes will still apply.
Technology: Multishot granted by Angelic Lyre's Blue and Red tunes will not apply; Yellow tune's barrage and cooldown will work, however.
Dr. Fetus: Angelic Lyre's tear modifier properties for each tune will apply to Dr. Fetus's bombs, including the multishot and barrage properties.
Void: Once absorbed, Angelic Lyre's tear modifiers won't apply until Void is used again. The tune will change each time Void is used.
Spindown Dice: Using Spindown Dice on Angelic Lyre will reroll it into 
Rat Poison, which can then be rerolled into 
Horncob, both of which are rare items.
Book of Virtues: Spawns a Blue, Red or Yellow music note wisp when Angelic Lyre is used, based on the tune. When a new wisp is spawned, any wisp spawned from the previous tune will be destroyed. There is no difference in behavior between any of the music note wisps.
Abyss: Spawns 3 Abyss Locusts that each look like blue, red and yellow music notes. The blue locust deals 1/3× damage and moves at default speed, the red locust deals 1× damage and moves at 25% speed, and the yellow locust deals 1/8× damage and moves at 200% speed.
