Raised for service during World War I, the battalion served in the trenches on the Western Front in France and Belgium from mid-1916 until the end of hostilities in November 1918.

The 45th Battalion was originally raised on 2 March 1916 as part of the expansion of the Australian Imperial Force (AIF) in Egypt, which was undertaken following the completion of the Gallipoli campaign.

[4] Its first major battle came at Pozières in August, where it undertook a defensive role, holding ground that had been captured by the Australian 2nd Division earlier in the fighting.

Later, after spending a period behind the lines near Ypres in Belgium, during the Battle of Bullecourt the battalion was held back in reserve and did not take part in the fighting.

[4] In March 1918, during the German spring offensive, the battalion repelled repeated attacks that were concentrated upon breaking through the Allied line at Dernancourt.

Following the end of hostilities, the demobilisation process began and the battalion's numbers fell as men were repatriated to Australia.

[6] In 2006, a critically acclaimed memoir by Edward Lynch (1898–1980), concerning his experiences as a private in 14 Platoon, D Company, 45th Battalion was published for the first time, under the title Somme Mud.

[6] Territorial designations were adopted in 1927 and the 45th Battalion assumed the title of the "St George Regiment";[2] its motto – Quo Fata Vocant – was also approved at this time.

[6] Initially, the Citizens Force was maintained through the compulsory training scheme, but after 1922 the battalion's authorised establishment was reduced in response to large-scale budget cuts that occurred following the Washington Naval Treaty.

[6] After the outbreak of World War II in 1939, Militia units were expanded through the re-establishment of conscription and took part in home defence duties and training.

[13] In December 1941, following Japan's entry into the war, the Militia were called up for full-time duty and the units of the 1st Division were tasked with the defence of the Sydney area.