Package delivery via autonomous drones is often presumed to hold commercial and societal value when applied to urban environments. However, to realise the benefits, the challenge of safely managing high traffic densities of drones in heavily constrained urban spaces needs to be addressed. This paper applies the principles of traffic segmentation and alignment to a constrained airspace in efforts to mitigate the probability of conflict. The study proposes an en-route airspace concept in which drone flights are directly guided along a one-way street network. This one-way airspace concept uses heading-altitude rules to vertically segment cruising traffic as well as transitioning flights with respect to their travel direction. However, transition flights trigger a substantial number of merging conflicts, thus negating a large part of the benefits gained from airspace structuring. In this paper, we aim to reduce the occurrence of merging conflicts and intrusions by using a delay-based and speed-based merge-assist strategy, both well-established methods from road traffic research. We apply these merge assistance strategies to the one-way airspace design and perform simulations for three traffic densities for the experiment area of Manhattan, New York. The results indicate, at most, a 9–16% decrease in total number of intrusions with the use of merge assistance. By investigating mesoscopic features of the urban street network, the data suggest that the relatively low efficacy of the merge strategies is mainly caused by insufficient space for safe manoeuvrability and the inability for the strategies to fully respond and thus resolve conflicts on short-distance streets.