Whilst there were many minor modifications on the series 2, many of these were under the skin. Maybe the only easy way so separate a Series 1 from a Series 2 is the adoption of opening rear quarter lights made with flat glass rather than curved. Also if a DB4 Series 2 is displayed with the bonnet up, it is clear that it is hinges from the front, a feature that was used right through to the end of production of derivatives of the Virage in 2000. The risk of a front opening bonnet is that if the catch was to fail, the bonnet could fly up at speed and obscure the drivers view of the road. The series 2 car also was fitted with uprated front brake callipers.

In order to aid vital engine cooling the sump was enlarged from 14 to 17 pints and the oil pump was also uprated. The much needed oil cooler was only an optional extra (indicated by a scoop under the front bumper) and was only fitted to a small number of cars at the time, although many have had them retrofitted more recently. Other options offered was overdrive and electric windows. Both Series 1 and 2 cars were fitted with the same rear Lucas light clusters as the DB Mark 3. These originated from the Humber Hawk but were also used on the Alvis TD21 and some special bodied Rolls Royce and Bentley motor cars. For some reason, this design are sometimes known as cathedral rear lights.

In total 349 of the Series 2 DB4 were built until the Series 3 was introduced in April 1961.