High-throughput image-based profiling platforms are powerful technologies capable of collecting data from billions of cells exposed to thousands of perturbations in a time- and cost-effective manner. Therefore, image-based profiling data has been increasingly used for diverse biological applications, such as predicting drug mechanism of action or gene function. However, batch effects pose severe limitations to community-wide efforts to integrate and interpret image-based profiling data collected across different laboratories and equipment. To address this problem, we benchmarked seven high-performing scRNA-seq batch correction techniques, representing diverse approaches, using a newly released Cell Painting dataset, the largest publicly accessible image-based dataset. We focused on five different scenarios with varying complexity, and we found that Harmony, a mixture-model based method, consistently outperformed the other tested methods. Our proposed framework, benchmark, and metrics can additionally be used to assess new batch correction methods in the future. Overall, this work paves the way for improvements that allow the community to make best use of public Cell Painting data for scientific discovery.