The street originates at Alaskan Way on the Seattle waterfront, and heads northeast through Downtown Seattle, First Hill, Capitol Hill, Madison Valley, Washington Park, and Madison Park, ending just east of 43rd Avenue East on Lake Washington.
For most of the run from Broadway to 12th Avenue, it forms the northern boundary of the Seattle University campus.
A cable car line provided public transportation along all or part of Madison Street from 1890 to 1940.
The line east from 21st to "Lake Washington and Madison Park" terminus opened in June 1891.
After the construction of a new powerhouse near 10th Avenue, the line from the downtown waterfront to 21st was cut back from the latter point to there in 1911, but the section between 10th and 14th was restored to operation in 1913.