It runs from the interchange Terbregseplein in the northeastern part of Rotterdam, towards the Belgian border near Hazeldonk.

Nearly the entire A16 motorway, including both the local and express lanes near Rotterdam, featured a maximum speed of 100 km/h.

At the section between the Moerdijk bridges and the Belgian border the maximum speed changed to 130 km/h as of 2011.

Between interchanges Klaverpolder and Zonzeel, the east–west A59 motorway follows the route of the A16 for about 8 kilometers.

Further south, between interchanges Princeville and Galder, the same goes for the (also east–west) A58 motorway, for a distance of about 6 kilometers.