Provided are a computer program product, system, and method for automating responses to expressions from an executing computer program. An automation object includes a plurality of expressions and corresponding responses, wherein at least one of the responses includes a response variable. A configuration object provides machine specific values for the response variables in the responses for a target computer on which the target computer program will execute. Compiled responses are generated by replacing the response variables in the responses with the machine specific values for the response variables provided in the configuration object for the target computer on which the target computer program will execute. The expressions in the automation object are processed to provide compiled responses for expressions received from the executing target computer program.