It was bounded by Bithynia on the east, Phrygia on the southeast, Lydia on the south, Aeolis on the southwest, Troad on the west, and the Propontis on the north.

[2] Under Augustus, Mysia occupied the whole of the northwest corner of Asia Minor, between the Hellespont and the Propontis to the north, Bithynia and Phrygia to the east, Lydia to the south, and the Aegean Sea to the west.

The major rivers in the northern part of the province are the Macestus and its tributary the Rhyndacus, both of which rise in Phrygia and, after diverging widely through Mysia, unite their waters below the lake of Apolloniatis about 15 miles (24 km) from the Propontis.

The Caïcus in the south rises in Temnus, and from thence flows westward to the Aegean Sea, passing within a few miles of Pergamon.

The whole sea-coast was studded with Greek towns, several of which were places of considerable importance; thus the northern portion included Parium, Lampsacus and Abydos, and the southern Assos, Adramyttium.

The narrative suggests that they were uncertain where to travel during this part of the journey, being "forbidden by the Holy Spirit to preach the word in Asia".