U.S. Route 52 (US 52) is a 166-mile (267 km) long United States highway in northeast Iowa. The route begins at the Savanna–Sabula Bridge over the Mississippi River between Sabula and Savanna, Illinois. From Sabula, it heads north along the Mississippi towards Bellevue and Dubuque. At Dubuque, US 52 briefly shares an expressway with U.S. Route 61 and U.S. Route 151.

North of Dubuque, the route follows the course of the river and turns to the west. At Luxemburg, it turns to the north towards Guttenberg. It then heads northwest where it overlaps U.S. Route 18 for 15 miles (24 km). At Calmar, US 52 turns to the north towards Decorah. US 52 crosses into Minnesota north of Burr Oak.

Despite its even number, US 52 is signed as a north–south route. According to the layout of the U.S. Highway System, even-numbered routes are generally signed as east–west routes.

U.S. Route 52 begins in Iowa with Iowa Highway 64 on the Savanna–Sabula Bridge over the Mississippi River north of Sabula. After descending the bridge, the two routes turn to the south and travel along a narrow, 2 + 1⁄2-mile (4.0 km) long causeway through the Mississippi backwaters. The two routes pass through Sabula, a city known as Iowa's island city, and turn west crossing another causeway to the mainland. Upon rising from the river valley, US 52 / Iowa 64 meet the northern end of U.S. Route 67. Iowa 64 continues west with US 67, while US 52 turns north to follow the river.

Between Sabula and Bellevue, US 52 follows the course of the Mississippi River. The roadway gradually enters the Driftless Area, a region of the midwestern United States which escaped glaciation during the last glacial period. Near the unincorporated community of Green Island, the highway passes through terrain where the elevation ranges from 600–800 feet (180–240 m) above sea level. North of Green Island, where it crosses the Maquoketa River, US 52 follows the bluffs along the Mississippi River valley. The Iowa, Chicago and Eastern Railroad (ICE Railroad) which runs parallel to US 52 between Green Island and Bellevue, in locations, lies 50 feet (15 m) below the road as the roadway follows the bluffs while the railroad tracks stay in the flat valley.

At Bellevue, US 52 runs along the city's riverfront and passes Lock and Dam No. 12. North of Bellevue, it turns to the northwest and rises 400 feet (120 m) in elevation and then descends 300 feet (91 m) at St. Donatus. North of St. Donatus, the highway travels 10 miles (16 km) and enters the Dubuque area and intersects U.S. Route 61 and U.S. Route 151.

The three routes head to the north towards downtown Dubuque. Shortly after a diamond interchange with Grandview Avenue, the three routes curve to the east and encounter a partial diamond interchange with Locust Street, which provides direct access to U.S. Route 20. The expressway curves back to the north, passes underneath the Julien Dubuque Bridge, and intersects a connector road which allows southbound traffic to access US 20. The expressway rises above ground level and heads towards Wisconsin, but US 52 exits at the 9th and 11th Streets exit. The exit also serves as the eastern end of Iowa Highway 3.

Through Dubuque, US 52 / Iowa 3 follow one-way streets for 1 + 1⁄4 miles (2.0 km). Northbound traffic follows 11th Street before turning onto White Street. Southbound traffic follows Central Avenue before turning onto 9th Street. The one-way streets realign onto Central Avenue, on which the routes stay for the rest of their time in Dubuque. South of Sageville, the two highways intersect Dubuque's Northwest Arterial, which carries Iowa Highway 32. North of Sageville, US 52 / Iowa 3 turn to the west along a particularly curvy and dangerous section of the road between Luxemburg and Dubuque. In a study conducted by the Center for Transportation Research and Education at Iowa State University, between 2002 and 2006, over 240 accidents with 6 fatalities occurred on this section. The road rises from the Driftless Area near Holy Cross and continues to Luxemburg.

At Luxemburg, US 52 and Iowa 3 split at an intersection with Iowa Highway 136. From Luxemburg, US 52 heads north towards Guttenberg. As it approaches the Mississippi River, the road reenters the Driftless Area. After crossing the Turkey River, the highway rises nearly 300 feet (91 m) in elevation before descending again at Guttenberg. North of Guttenberg, US 52 rises out of the Mississippi valley and travels west and then northwest away from the river. North of Garnavillo, it intersects Iowa 128, which serves as a cutoff to Iowa 13 near Elkader. Eight miles (13 km) later, it intersects Iowa 13 at its northern end.

One mile (1.6 km) north of the Iowa 13 intersection, US 52 intersects U.S. Route 18. Between this location and Calmar, US 52 runs parallel to the ICE Railroad. The two highways travel together to the northwest for 17 miles (27 km) through Monona and Postville. At Postville, US 18 / US 52 intersect Iowa Highway 51. On the west side of Postville, US 52 splits away from US 18 and heads to the northwest towards Calmar. At Calmar, US 52 turns to the north at an intersection which is also the eastern end of Iowa Highway 24 and the northern end of Iowa Highway 150. It heads to the north-northeast for 9 miles (14 km) to an intersection with Iowa Highway 9 on the southwest side of Decorah. From Iowa 9, the route crosses the Upper Iowa River near the Luther College campus. It heads north past the unincorporated community of Burr Oak. 2 miles (3.2 km) north of Burr Oak, US 52 crosses the state line into Minnesota.

U.S. Route 52 was designated in Iowa in 1935, replacing U.S. Route 55 from Primary Road No. 117 near Sabula to the Minnesota state line north of Burr Oak. US 52 crossed the Mississippi River at the recently-constructed Savanna–Sabula Bridge, which opened in 1932. The section of old-US 55 from Primary Road No. 117 to Dubuque was overlapped by U.S. Route 67 until 1967 when US 67 was truncated back to the intersection with US 52 on Iowa 64.

From 1963 to 1967, US 52 was realigned from Dubuque to Luxemburg to follow U.S. Route 20 to Dyersville and Iowa Highway 136 to Luxemburg while its original alignment was rebuilt. During this time, Iowa 136, which ended at US 52 in Luxemburg, was truncated back to US 20 at Dyersville, but it was redesignated along this segment after US 52 returned to its old alignment.

In the mid-1990s, US 52 / US 61 / US 151 in Dubuque were shifted onto a new expressway through downtown Dubuque, which caused the three U.S. highways to no longer intersect US 20 directly. Iowa Highway 946 was designated as a connector route to provide direct access to US 20 from the three U.S. highways.

Iowa Highway 946's short route begins at a partial trumpet interchange along the US 52 / US 61 / US 151 expressway. Northbound traffic passes beneath the expressway and joins southbound traffic on Locust Street. In the half-mile (800 m) between US 52 / US 61 / US 151 and US 20, Iowa 946 passes a light industrial area containing a Hy-Vee grocery store.

Iowa 946 intersects U.S. Route 20, known locally as Dodge Street, at a signal-controlled intersection. Immediately east of this intersection is the approach to the Julien Dubuque Bridge, which carries US 20 across the Mississippi River into East Dubuque, Illinois. Iowa 946 continues north on Locust for 1,000 feet (300 m) through another light industrial area. At the edge of downtown Dubuque, Highway 946 turns east for 600 feet (180 m) where it meets US 52 / US 61 / US 151 just west of Dubuque's Ice Harbor.

Iowa 946 was created along Locust Street upon the completion[when?] of an expressway which relocated U.S. Route 52, U.S. Route 61, and U.S. Route 151 away from Locust Street and closer to the Mississippi River. The new expressway carried the three routes beneath the approach to the Julien Dubuque Bridge, making a direct intersection impossible. Since all four routes are U.S. Highways and come from all directions, it was imperative to keep the routes connected.