In a game as notoriously difficult as Enter the Gungeon, you need whatever edge you can get; one of the best being synergies. Synergies occur when two items work to better each other, whether it be increasing gun damage or item potency. Of the gungeon's synergies, there are some that have meager effects, while others are an incredible help.

5. Jolly Roger (Skull Splitter + VertebraeK-47)

The combo that got me to the High Dragun with minimal experience, the Jolly Roger is an overpowered delight; and one you can get early on.

The two bone-themed guns are powerful on their own and even more-so together. What makes this synergy so powerful is specifically how the VertebraeK-47 affects the Skull Splitter.

The Jolly Roger links together skull-bullets that the Skull Splitter fires, turning shots into a 3-skull chain that you can use to spam enemies to hell. On the other hand, the VertebraeK-47 is able to freeze enemies with this combo. If you’re able to pick up ammo reloads along your way all you will need is this gun to pass through 95% of enemies.

4. Ice Water (Snowballer + Mega Douser)

    If you’re ever wanted to shoot ice water at your enemies until they cease to be, I’ve got a synergy for you. Ice Water is a powerful upgrade to the Mega Douser, a water gun that you can get fairly easy alongside another gun that shows up often.

    While both guns deal an additional 30% damage when paired together, it’s what happens to the Mega Douser that makes this combo worth pursuing. Ice Water causes the Mega Douser’s water to freeze enemies, making them move slower, and increases the size of the gun’s water stream.

    If you get Ice Water, you can knock back most enemies you come across with its considerable force, getting them out of the way so you can blast them with your other absurd combinations. It’s a practical synergy you can use against anything and everything, and that is why it makes the list.

3. Knight Time (Ballistic Boots + Gunknight Greaves)

    The only synergy on this list that isn’t a gun, it deserves Top 3 placement not just for its usefulness on a run, but for how fun it is to have. With Knight Time, time briefly stops whenever you take damage.

    While it’s usefulness is singular, it’s an amazing feeling to shoot up your enemies whenever you get hurt like you’re Quicksilver in Days of Future Past. If you have an overpowered weapon, you can take a hit and then get in a shot with no resistance at all. If you need to escape from a hoard of Gunzookie, you can take the hit and escape. The limits are the imagination in this case.

    For letting you feel like an anime character, even for a “brief” time, Knight Time gets 3rd place on this list.

2. Great Queen Ant (Gungeon Ant + Gilded Bullets, Coin Crown, Heck Blaster, Crown of Guns, or Ring of Fire Resistance) 

    Arguable the grossest synergy on this list, the Great Queen Ant gets 2nd place for how powerful this combo is in terms of damage.

    One of the main downsides to having the Gungeon Ant is its alternating fire, switching between fireballs and oil whenever you reload. What the Great Queen Ant does is it gets rid of the oil and replaces it with exploding ants that destroy enemy bullets that get caught in their explosions.

This is useful in a similar sense to Knight Time, allowing you to get out of situations when you’re gunned down and against the wall, without the downside of having to get yourself hurt. It’s also useful against bosses that spam you with gigantic walls of bullets that require perfect reaction-time to dodge. In that sense, this synergy makes for an incredibly useful tool to get out of bad situations and gets rid of the Gungeon Ant’s main annoyance. 

1. Betrayer’s Lies (Betrayer’s Sheild + Lies)

    This gun is perfect for those who like playing offensively and perhaps more-so defensively. Increasing the capabilities of Betrayer’s Shield (a gun you can get after defeating Blocker, a hidden boss found in the Black Powder Mines), you can go a long way and perhaps to the end with this gun. 

Specifically, in addition to the shield that Betrayer’s Lies drops on reload when synergized with Lies (a passive item only useful as a part of synergies) the gun gains infinite ammo, a larger magazine, increased accuracy, and higher fire rate. This is a synergy that’s perfectly balanced with offense and defense, one that you can use to camp behind your shield and shoot the hell out of whatever’s in your way; not to mention you could use the gun to drop a shield and fire your bazooka or whatever your heavy-hitter gun is at enemies.

For its balance and sheer power, Betrayer’s Lies is the best synergy in Enter the Gungeon.

Also Be Sure To Read:

• [Top 10] Enter the Gungeon Best Mods Every Player Should Use
• [Top 5] Enter The Gungeon Best Guns
•  
• [Top 10] Enter The Gungeon Best Items
• [Top 5] Enter The Gungeon Best Synergies
•  
• [Top 5] Enter The Gungeon Best Characters
• Top 10 Games Like Enter The Gungeon (Games Better Than Enter The Gungeon In Their Own Way)