An appropriate sequence of assembly operations increases the productivity and enhances product quality there by decrease the overall cost and manufacturing lead time. Achieving such assembly sequence is a complex combinatorial optimization problem with huge search space and multiple assembly qualifying criteria. The purpose of the current research work is to develop an intelligent strategy to obtain an optimal assembly sequence subjected to the assembly predicates. This paper presents a novel hybrid artificial intelligent technique, which executes Artificial Immune System (AIS) in combination with the Genetic Algorithm (GA) to find out an optimal feasible assembly sequence from the possible assembly sequence. Two immune models are introduced in the current research work: (1) Bone marrow model for generating possible assembly sequence and reduce the system redundancy and (2) Negative selection model for obtaining feasible assembly sequence. Later, these two models are integrated with GA in order to obtain an optimal assembly sequence. The proposed AIS-GA algorithm aims at enhancing the performance of AIS by incorporating GA as a local search strategy to achieve global optimum solution for assemblies with large number of parts. The proposed algorithm is implemented on a mechanical assembly composed of eleven parts joined by several connectors. The method is found to be successful in achieving global optimum solution with less computational time compared to traditional artificial intelligent techniques. © 2017 Growing Science Ltd. All rights reserved and 2016 by the authors; licensee Growing Science, Canada.