To address the challenges of poor trajectory accuracy in industrial robots, which has emerged as a technological bottleneck hindering further robots’ applications in high-precision manufacturing industries, this paper proposes a method for the analysis and reliability-based optimization design for industrial robots’ trajectory accuracy considering parametric uncertainties. Firstly, the dynamic equation of an articulated industrial robot with six degrees of freedom is derived, incorporating the Stribeck joint friction model, followed by the uncertain parameter identification of this dynamic model. Subsequently, an uncertainty simulation system for the robot is established based on the constructed dynamic model and the sensitivity of system uncertain parameters to the robot trajectory accuracy is analyzed, where 10 key parameters are obtained among 54 uncertain parameters. Finally, a reliability-based multi-objective optimization design methodology is proposed synthesizing the robot trajectory accuracy, manufacturing cost, and quality loss, to achieve tolerance design of the robot's parameters, and enables minimizing costs and quality losses while ensuring the robot's trajectory accuracy reliability. The performance and practicality of the proposed method were validated using a six-degree-of-freedom rotary joint serial industrial robot as an example.