The James Webb Space Telescope is NASA’s flagship mission and successor to the highly successful Hubble Space Telescope. It is an infrared observatory featuring a cryogenic 6.6 m aperture, deployable optical telescope element with a payload of four science instruments assembled into an integrated science instrument module that provide imagery and spectroscopy in the near infrared band between 0.6 and 5 μm and in the mid-infrared band between 5 and 28 μm. JWST was successfully launched on December 25, 2021, aboard an Ariane 5 launch vehicle. All 50 major deployments were successfully completed by January 8, 2022. The observatory performed all mid-course correction maneuvers and achieved its operational mission orbit around the Sun-Earth second Lagrange Point. All commissioning and calibration activities have been completed and JWST has begun its science mission. Its present performance meets or out-performs all requirements. Launching over 20 years after its mission concept review, the JWST Observatory is a first and only of its kind of facility. This program faced many unique challenges that were not only technical in nature but also organizational and managerial. We describe the challenges faced by the JWST systems engineering team, the way the team addressed them, and make recommendations for focus areas of future flagship missions, which will likely face similar challenges. It will not explicitly address the cost challenges of the mission. We first describe the mission and its over-arching challenges. We then describe the tailoring of systems engineering processes and methods used to address these challenges and effectiveness. The events, tasks, issues, and their resolutions and the resulting specific lessons learned from the project are discussed with the over-arching recommendations for future flagship missions that derive from these lessons.