Substrate effects on the mechanical properties and contact damage of diamond-like carbon (DLC) films have been investigated. To that end, a DLC film of 1 μm thickness was deposited on two different substrates: soda–lime glass (compliant and soft), and single-crystal silicon (stiff and hard). The elastic modulus and hardness were measured by means of nanoindentation. Quasi-static and sliding contact configurations were simulated by means of ultra-micro indentation, and surface and cross-sectional damage were assessed using a focused ion beam (FIB) miller. It was found that a compliant and soft substrate enhances crack initiation on the film surface in the form of ring/cone cracks. On the other hand, a stiff and hard substrate delays crack initiation in the film, but is more susceptible to fracture in the form of median and lateral cracks due to increased brittleness. The results have implications for the reliability of DLC-coated systems.