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Following the two-liter restriction on engine displacement, Miller fitted a new engine into his successful Indianapolis design. Like the 183 it replaced, the 122 featured a four-cylinder engine the was beautifully executed. Almost the entire car used castings and designs from Miller which were created at the highest level but came at a very high cost.

The entire car was sketched by Leo Goossen and Harry A. Miller which were translated into aluminum, bronze and steel at his foundry run by Fred Offenhauser. As a result the car was almost 100% unique, only relying on outsourcing the wheels, tires, gauges and ignition system.

For the 1923 season a new two-liter engine was created with a bore and stroke of 2.334 by 3.5 inches. The cylinder heads were cast integrally with the cast iron cylinder block and sat a on a common aluminum crankcase. Like most Millers the 122 used a double overhead camshaft setup which was first copied from the 1913 Peugeot Grand Prix car. This allowed for hemispherical combustion chambers. With 5-main bearings and two valves per cylinder around 150 bhp was available. This increased to 235 bhp at 5800 with a supercharger first fitted in 1925.

A very thin chassis was built up for the 122 that had an equally narrow bodywork. The bodywork was only 18 inches wide and the entire car weighed only 1350 lbs. This resulted in a top speed of 141.17 mph (227.14 kph).

On the track Millers dominated Indianapolis and the 122 won on its first attempt in 1923. A total of seven 122s were prepared for the 1923 Indianapolis 500, five of which were owned by William Crapo Durant. Tommy Milton went on to win the Indy driving for the H.C.S. Motor Co.

Around 15 model 122s were made. Three model 122s were sent to Europe to race in the Grand Prix. Two very special cars were fabricated with front-wheel drive (FWD) in 1924 that would motivate many more FWD and 4WD Millers. These are distinguished by their front-mounted differential and much lower bodywork.

By 1926, the Miller 122 was rendered obsolete by the 91 in³ (1.5 liter). Some 122 cars were converted into type 91s.