Derfflinger was completed shortly after the outbreak of World War I in 1914; after entering service, she joined the other German battlecruisers in I Scouting Group of the High Seas Fleet, where she served for the duration of the conflict.

These operations culminated in the Battle of Jutland on 31 May – 1 June 1916, where Derfflinger helped to sink the British battlecruisers HMS Queen Mary and Invincible.

As a result, Derfflinger and the rest of the High Seas Fleet saw little activity for the last two years of the war apart from patrol duty in the German Bight.

On the order of Rear Admiral Ludwig von Reuter, the interned ships were scuttled on 21 June 1919 to prevent them from being seized by the Allied powers.

To keep costs from growing too quickly, the number of guns was reduced from ten to eight, compared to the earlier Seydlitz, but a more efficient superfiring arrangement was adopted.

As Europe drifted toward war during the July Crisis, the German naval command issued orders on the 27th placing the fleet on a state of heightened alert, though Derfflinger was not yet complete.

The ship's first wartime operation took place on 20 November; Derfflinger sortied with the light cruisers Stralsund and Strassburg and V Torpedoboat Flotilla for a sweep some 80 nautical miles (150 km; 92 mi) northwest of the island of Helgoland.

Following Seydlitz were Derfflinger, Moltke, Von der Tann, and Blücher, along with the light cruisers Kolberg, Strassburg, Stralsund, and Graudenz, and two squadrons of torpedo boats.

Admiral Ingenohl was initially reluctant to attempt to destroy these forces, because I Scouting Group was temporarily weakened while Von der Tann was in drydock for periodic maintenance.

Konteradmiral Richard Eckermann, the Chief of Staff of the High Seas Fleet, insisted on the operation, and so Ingenohl relented and ordered Hipper to take his battlecruisers to the Dogger Bank.

[17] On 23 January, Hipper sortied, with Seydlitz in the lead, followed by Moltke, Derfflinger, and Blücher, along with the light cruisers Graudenz, Rostock, Stralsund, and Kolberg and 19 torpedo boats from V Flotilla and II and XVIII Half-Flotillas.

At 11:18, two of Derfflinger's 12 in (30 cm) shells hit Lion, one of which struck the waterline and penetrated the belt, allowing seawater to enter the port feed tank.

Beatty, in the stricken Lion, ordered the remaining battlecruisers to "engage the enemy's rear," but signal confusion caused the ships to solely target Blücher, allowing Moltke, Seydlitz, and Derfflinger to escape.

Derfflinger, her newly commissioned sister ship Lützow, and the veterans Moltke, Seydlitz and Von der Tann left the Jade Estuary at 10:55 on 24 April.

[25] The heavy units of the High Seas Fleet, under the command of Admiral Reinhard Scheer, sailed at 13:40, with the objective to provide distant support for Boedicker's ships.

At 15:38, Seydlitz struck a naval mine, which tore a 15 metres (50 ft) hole in her hull, just abaft the starboard broadside torpedo tube, allowing 1,300 tonnes (1,400 short tons) of water to enter the ship.

At a range of approximately 13,000 m (14,000 yd), the German battlecruisers destroyed two 150 millimetres (6 in) shore batteries and inflicted other damage to the town, including the destruction of some 200 houses.

Due to reports of British submarines and torpedo attacks, Boedicker broke off the chase and turned back east towards the High Seas Fleet.

He had initially intended to launch the operation in mid-May, but the mine damage to Seydlitz had proved difficult to repair, and Scheer was unwilling to embark on a major raid without his battlecruiser forces at full strength.

[31] Shortly thereafter the second half of Beatty's force, the four Queen Elizabeth-class battleships of the 5th Battle Squadron, came into range and began firing at Von der Tann and Moltke.

[33] The leading ships of the German High Seas fleet had by 18:00 come within effective range of the British battlecruisers and Queen Elizabeth-class battleships and had begun trading shots with them.

[39] Instead, Scheer ordered his ships to turn 16 points to starboard, which would bring the pre-dreadnoughts to the relative safety of the disengaged side of the German battle line.

[48] In the ensuing melee, Derfflinger was hit several times; at 21:34, a heavy shell struck her last operational gun turret and put it out of action.

By that time, Derfflinger and Von der Tann had only two operational guns each, Moltke was flooded with 1,000 tons of water, Lützow had sunk, and Seydlitz was severely damaged.

[51] Hipper reported: "I Scouting Group was therefore no longer of any value for a serious engagement, and was consequently directed to return to harbor by the Commander-in-Chief, while he himself determined to await developments off Horns Reef with the battlefleet.

[56] During the Second Battle of Heligoland Bight in November 1917, Derfflinger sailed from port to assist the German light cruisers of II Scouting Group, but by the time she and the other battlecruisers arrived on the scene, the British raiders had fled northward.

[60] At 06:10 the German battlecruisers had reached a position approximately 60 kilometers (37 mi) southwest of Bergen when Moltke lost her inner starboard propeller, which severely damaged the ship's engines.

As Derfflinger and Von der Tann passed through the locks that separated Wilhelmshaven's inner harbor and roadstead, some 300 men from both ships climbed over the side and disappeared ashore.

[64] Following Germany's capitulation, the Allies demanded that the majority of the High Seas Fleet be interned in the British naval base at Scapa Flow pending an ultimate resolution of their fate.

One of the ship's bells was delivered to the German Federal Navy on 30 August 1965;[70] the other is exhibited outside St Michael's Roman Catholic Church on the Outer Hebrides island of Eriskay.