While the immune system is involved in some way, the exact cause of eczema is unknown. Typically, contact with some external allergen triggers an allergic reaction, leading to the typical skin symptoms and changes seen in eczema. This contact may occur once and result in symptoms, or may be repeated over a long period of time, with cumulative exposure finally resulting in eczema.

A number of factors increase the risk of a person getting eczema. While people of any age can get eczema, it is most common in babies and young children. About one-third of all eczema patients develop symptoms before their first birthday, and almost all develop symptoms before five years. Genetic factors are also thought to play a key role, but these are not well understood. What is known is that eczema is more common in people with a family history of eczema. People who have a pre-existing allergic condition, such as hay fever, sinusitis, or allergies to plant pollens or animal dander, are more likely to develop eczema. Other medical conditions, such as respiratory infections, may also act as triggers. Studies have also shown that eczema may be more common in babies who suffer from allergic rhinitis or food allergies, or whose mothers suffer from asthma.

Environmental factors are implicated in many cases of eczema. Such factors include extreme temperatures, or exposure to a large number of skin irritants. Some known environmental triggers of eczema include detergents, bath and beauty products, chemical compounds like nickel and cobalt, certain foods, and certain types of fabric. Emotional stress can also trigger eczema. Some scientific studies have shown that eczema in babies is linked to early weaning; continued breastfeeding may therefore be protective in some way.