The potential for replacing the fossil-based Polyoxymethylene (POM) and Polyamide 66 (PA 66) in polymer gear applications with a bio-based Polyamide 6.10 (PA 6.10) was studied and is presented in the article. The use of bio-based plastics is increasing but mostly in undemanding applications like packaging. High-performance plastics are needed in polymer gear transmissions since their operational conditions are far more severe. The potential of bio-based PA 6.10 was studied by means of gear lifespan testing. Additional insights into the process of polymer gear meshing were garnered by simulating all the tested cases with a FEM model of meshing gears. Test gears were manufactured from commercially available materials, making the results useful for gear designers. Encouraging results were observed since the PA 6.10 gears exhibited a 3.5-times longer lifespan than POM gears and a 10-times longer lifespan than PA 66 gears when tested under identical test conditions. The results indicate great potential for replacing fossil-based plastics in polymer gear applications with bio-based polymer materials. The fatigue strength, coefficient of friction, and wear coefficient were determined and compared for the tested materials, facilitating the reliable design of polymer gears.