On commissioning, E4 joined the 8th Submarine Flotilla as part of the Home Fleets, and was inspected by King George V at Portsmouth.

[4][5] E4 remained part of the 8th Submarine Flotilla, based at Portsmouth on the eve of the outbreak of the First World War in August 1914.

[10] On 28 August 1914, E4 was one of eight submarines that took part in a raid against the German Heligoland Bight patrol by the Harwich Force.

E4, short of space, also picked up three German survivors, leaving the remainder in a boat with provisions and a compass.

[16] On 21 May 1915, E4 left Harwich to patrol North of Helgoland, to attack German minesweepers which were thought to be clearing a British minefield.

[17] On 24 July, E4 set out on a patrol off the Horns Reef, and later that day sighted a submarine near the North Hinder lightvessel.

On 28 July E4 was attacked off Horns Reef by two German Vorpostenboot, Senator von Berenburg Goszler and Harry Busse.

E4 picked up 11 survivors from the sunken trawler, taking three of them prisoner, and landing the others on the Horns Reef lightvessel.

On 1 September, E4 and E6 set out from Harwich to the Western side of the German Bight on an anti-Zeppelin patrol.

[23] E4, by now fitted with two 3-inch (76 mm) anti-aircraft guns, continued to carry out anti-Zeppelin patrols in May 1916, being near-missed by two bombs dropped by a German airship on 20 May.

[27] E4 remained part of the 9th Flotilla until the end of the war,[28] although she was noted as being paid off in December 1918.