US 45 travels concurrently with State Route 17 (SR 17) from its southern terminus to just north of Deer Park.

US 45 begins at the intersection of St. Stephens Road and Spring Hill Avenue west of downtown Mobile.

Spring Hill Avenue carries US 98 to the east and west while St. Stephens Road heads to the northwest through the city and into Prichard.

It curves to the north and northwest as it travels through Mauvilla, Chunchula, and Citronelle.

Just north of Deer Park, SR 17 splits off to the northeast toward Chatom at a Y intersection.

The highway curves back to the northwest and goes through Fruitdale and later Yellow Pine.

The entire highway was an "existing road upon which the state has done no work" except for a segment from just north of Gulfcrest to Fruitdale, which was indicated to be graded.

[13][14] By the end of 1934, US 43, along with SR 5 were designated in Mobile, but the state maps are unclear as to whether they traveled concurrently with US 45/SR 57.

[19][20] By 1941, the highway was indicated to be under construction from just southeast of Fruitdale to just northwest of Yellow Pine.