This paper presents the development of a multilevel optimization framework for the design and selection of departure routes, and the distribution of aircraft movements among these routes, while taking the sequence and separation requirements for aircraft on runways and along selected routes into account. The main aim of the framework is to minimize aircraft noise impact on communities around an airport, and the associated fuel consumption. The proposed framework features two consecutive steps. In the first step, for each given Standard Instrument Departure (SID), multi-objective trajectory optimization is utilized to generate a comprehensive set of possible alternative routes. The obtained set is subsequently used as input for the optimization problem in the second step. In this step, the selection of routes for each SID and the distribution of aircraft movements among these routes are optimized simultaneously. To ensure the feasibility of optimized solutions for an entire operational day, the sequence and separation requirements for aircraft on runways and along selected routes are included in this second phase. In order to address these issues, three novel techniques are developed and added to a previously developed multilevel optimization framework, viz., a runway assignment model, a conflict detection algorithm, and a rerouting technique. The proposed framework is applied to a realistic case study at Amsterdam Airport Schiphol in the Netherlands, in which 599 departure flights and 13 different SIDs are considered. The optimization results show that the proposed model can offer conflict-free solutions, one of which can lead to a reduction in the number of people annoyed of up to 21%, and a reduction in fuel consumption of 8% relative to the reference case solution.