Government Street begins at the intersection with the Old Spanish Trail on Blakeley Island, east of where it emerges from the Bankhead Tunnel.

It then continues for approximately 10 miles (16 km) until it ends at the southwesternmost limits of the city, in Theodore.

The street was laid out and named after the close of Mobile's colonial era, following the demolition of the obsolete Fort Conde.

In the early 1820s the marshlands between the Mobile River and Royal Street were filled in with the bricks and other material from the demolished fort.

The area east of Houston Street still has many 19th- to early 20th-century mansions that date back to the time when Government was the most prestigious address that one could have in Mobile.