Alongside detachments from the Einsatzgruppen and the SS Cavalry Brigade, it perpetrated mass murders and was responsible for large-scale crimes against humanity targeting civilian populations in the course of the Nazi security warfare.

The scope of the regiment's operations was known to British intelligence since July 1941 but, for reasons of national security, information pertaining to their activities was not released until 1993.

[2] Twenty-three Order Police battalions were slated to take part in the 1941 invasion of the Soviet Union, Operation Barbarossa.

Two battalions were assigned to support the Einsatzgruppen, the mobile death squads of the SS, and the Organisation Todt, the military construction group.

The goals of the Order Police battalions were to secure the rear by eliminating the remnants of the enemy forces, guarding the prisoners of war, and protecting the lines of communications and captured industrial facilities.

When it crossed the German-Soviet border, the regiment came under the control of Erich von dem Bach-Zelewski, the Higher SS and Police Leader (HSS-PF) for Army Group Centre.

[6] Himmler made a personal visit to the headquarters of the unit in Belostok on 8 July where he met with Max von Schenckendorff, commander of Army Group Centre Rear Area, Daluege, Montua, Bach-Zalewski, and the regiment's officers.

[8] The next day, 9 July, Police Battalion 307 participated in the massacre of 4–6,000 Jewish men, Russians and Belarusians in the vicinity of Brest-Litovsk (now Brest, Belarus).

[7] On 10 July, Daluege addressed the members of the regiment arrayed in a parade formation, extolling them to "exterminate" Bolshevism as a "blessing for Germany".

[10] On 11 July, Montua passed a confidential order from Bach-Zalewski to the battalion commanders that Jews, who had been "convicted of looting", were to be shot; an execution took place the same day.

[13] In September 1941, the regiment participated in the Mogilev conference, organised by General Max von Schenckendorff, commander of the Army Group Centre Rear Area.

On the second day, participants travelled to a nearby settlement where a company of Police Battalion 322, assisted by the troops of the SD, conducted a demonstration of how to surround and screen a village.

[23] Progress reports on the murderous activities of the Police Regiment Center, the Einsatzgruppen detachment and the SS Cavalry Brigade were regularly forwarded by Bach-Zalewski.

Angered by the scope of the atrocities, Churchill delivered a speech over the radio on 24 August stating:[24] Whole districts are being exterminated (...) Scores of thousands of executions are perpetrated by the German police troops upon the Soviet patriots defending their native soil.

We are in the presence of a crime without a name.From 27 August, Bletchley Park delivered specially prepared daily intelligence reports on the activities of the police troops.

On 12 September, the German Police changed their cipher; the following day, the SS officials were instructed to stop transmitting the reports over the radio.