With nearly 1 million observations of column-mean carbon dioxide concentration (X (Formula presented.)) per day, the Orbiting Carbon Observatory 2 (OCO-2) presents exciting possibilities for monitoring the global carbon cycle, including the detection of subcontinental column CO2 variations. While the OCO-2 data set has been shown to achieve target precision and accuracy on a single-sounding level, the validation of X (Formula presented.) spatial gradients on subcontinental scales remains challenging. In this work, we investigate the use of an integrated path differential absorption (IPDA) lidar for evaluation of OCO-2 observations via NASA's Atmospheric Carbon and Transport (ACT)-America project. The project has completed eight clear-sky underflights of OCO-2 with the Multifunctional Fiber Laser Lidar (MFLL)—along with a suite of in situ instruments—giving a precisely colocated, high-resolution validation data set spanning nearly 3,800 km across four seasons. We explore the challenges and opportunities involved in comparing the MFLL and OCO-2 X (Formula presented.) data sets and evaluate their agreement on synoptic and local scales. We find that OCO-2 synoptic-scale gradients generally agree with those derived from the lidar, typically to ±0.1 ppm per degree latitude for gradients ranging in strength from 0 to 1 ppm per degree latitude. CO2 reanalysis products also typically agree to ±0.25 ppm per degree when compared with an in situ-informed CO2 “curtain.” Real X (Formula presented.) features at local scales, however, remain challenging to observe and validate from space, with correlation coefficients typically below 0.35 between OCO-2 and the MFLL. Even so, ACT-America data have helped investigate interesting local X (Formula presented.) patterns and identify systematic spurious cloud-related features in the OCO-2 data set.