Special routes of U.S. Route 61

Natchez business loop

US 61 BUS in Natchez, MS uses part of US 425/US 84, then turns onto Homochitto Street. US 61 BUS turns right onto South Martin Luther King Jr. Street. US 61 BUS then turns onto a pair of one way streets concurrent with US 84 BUS (East Franklin Street northbound; Saint Cathrine Street southbound); Mississippi Highway 555 continues northward. The routes then merge into a divided highway before meeting mainline US 61/US 84.

Keokuk business loop

U.S. Route 61 BUS in Keokuk, Iowa travels concurrent with US 136 and US 218 for its entire length. US 61 uses a more direct bypass alignment to the northwest of downtown Keokuk.

Fort Madison business loop

U.S. Route 61 Business was created through Fort Madison, Iowa, along the former routing of US 61. The main route was rerouted around town along a new four-lane bypass in 2012. It begins at the interchange with Iowa Highway 2 (Iowa 2) west of Fort Madison. The two routes run east together into town. Iowa 2 splits away to cross the river near downtown and the route turns north and heads out of town. It ends at another interchange with US 61 northeast of town. From 2011 to 2013, the portion of highway north of Iowa 2 was known officially as Iowa 961, but it was not signed as such.

Muscatine business loop

U.S. Highway 61 Business was created in 1984 after U.S. Highway 61 (US 61) was rerouted around Muscatine on a new four-lane bypass. It begins on the southern edge of Muscatine at the intersection of US 61 and Iowa Highway 92 (Iowa 92). US 61 Business heads north through Muscatine's industrial area and into the downtown riverfront. It is joined by Iowa 38 and Iowa 92 at an intersection near the foot of the Norbert F. Beckey Bridge. The intersection marks the southern end of Iowa 38 while Iowa 92 crosses the bridge into Illinois. A few blocks later, the three routes are joined by Iowa 22. All four routes continue north for a mile before meeting US 61.

The entire route is in Muscatine, Muscatine County.

Davenport business loop

U.S. Route 61 Business was created in 2010 when U.S. Route 61 was rerouted around Davenport on I-280 and I-80. The route begins on the southwest end of town at the interchange with I-280. From there, it heads towards the Mississippi River along River Drive. For six blocks, US 61 Bus. is overlapped by US 67, which joins from the south at the Centennial Bridge and parts to the north when US 61 Bus. turns off. For the most of the remaining trip through Davenport, the route runs along two one-way streets: Brady Street (northbound) and Harrison Street (southbound). Near 5th Street in downtown Davenport, the Iowa Interstate Railroad crosses over Brady and Harrison streets. The vertical clearance of both bridges is only 11 feet 8 inches (3.56 m), which causes many trucks that attempt to pass beneath the bridge to hit or become stuck. This bridge was a major factor in US 61's realignment. Just south of Kimberly Road, which carries US 6, the southbound lanes of US 61 Bus. turn onto Harrison Street from Welcome Way. North of 53rd Street, the two directions rejoin as one road. The route ends at the I-80 interchange on the northern side of town. The entire route is inventoried as Iowa Highway 461, but it not signed as such.

The entire route is in Scott County.

Maquoketa business loop

The business route through Maquoketa follows Main Street through the downtown business district, and Iowa Highway 64 along Platt Street. The route is unsigned, aside from a few circle "City Route 61" signs along Main Street.

Although not designated until 1998, Main Street had essentially served as a "Business 61" since at least the mid-1970s, when U.S. 61 was moved to a two-lane bypass around the south and west parts of the city. The two-lane segment was upgraded to four lanes in the summer of 1996, as part of a massive four-lane project of U.S. 61 between Dubuque and De Witt.