Lipson's work focuses on evolutionary robotics, design automation, rapid prototyping, artificial life, and creating machines that can demonstrate some aspects of human creativity.

[3] Lipson has been involved with machine learning and presented his "self-aware" robot at the 2007 TED conference.

[6] Beginning in 2009, he and his Cornell University graduate student Michael Schmidt developed a software named Eureqa[7] capable of deriving equations, mathematical relationships and laws of nature from sets of data: for instance, deriving Newton's second law of motion from a data set of positions and velocities of a double pendulum.

[8][9] In 2011, it was reported that Eureqa had succeeded at a much more complex task: re-deriving seven equations describing how levels of various chemical compounds fluctuate in oxygen-deprived yeast cells.

[10] In research on robotic self-awareness he advocates "self-simulation" as preliminary stage.