Otto had been drafted twice before, but sent home as "Not fit for service at present underweight!". But in May 1940, Otto was finally drafted into the 104th Infantry Replacement Battalion. Following training, he volunteered for the Panzer Corps. Otto learned the fundamentals of tank warfare at Putlos in Holstein as a member of the 7th Panzer Replacement Battalion.

His unit was integrated into the newly formed 21st Panzer Regiment and June 1941, was sent to East Prussia. He experienced his first battle as a gunner in a Panzer 38(t) during Operation Barbarossa in late June 1941. It was during this operation that Carius suffered wounds from a round that struck his tank.

In 1943, Carius transferred to the schwere Panzer-Abteilung 502 (502 heavy tank battalion). This unit fought at the Leningrad front and then in the area of Narva, Estonia (Battle of Narva). Carius was severely wounded on July 24, 1944 while reconnoitering a village on a motorcycle ahead of his tanks. Until that day, he was unofficially running the 2nd company of 502nd, however, he officially became the commander of 2nd company on the same day he got shot through the leg, arm, 4 bullets in the back and one through the neck. He subsequently became the commander of a Jagdtiger company of the 512th Heavy Antitank Battalion (schwere Panzerjägerabteilung) in the West at the beginning of 1945. On 8 March 1945, without finishing its training, 2nd company was directed to the front-line near Siegburg. It then took part in the defense of the River Rhine and eventually surrendered to the US Army on 15 April 1945.

Otto Carius is credited with the destruction of more than 150 enemy tanks and is one of the highest scoring tank aces in history.