U.S. Route 69 is a north–south United States highway. When it was first created, it was only 150 miles (241 km) long, but it has since been expanded into a Minnesota to Texas cross-country route. The highway's southern terminus (as well as those of US 287 and US 96) is in Port Arthur, Texas at an intersection with State Highway 87. Its northern terminus is in Albert Lea, Minnesota at Minnesota State Highway 13. US 69 is a noteworthy victim of sign theft because of the sexual connotation of its route number.[citation needed]

US 69 begins at its southern terminus with SH 87 and SH 347 in Port Arthur. This intersection is also the southern terminus for US 96 and US 287, which are concurrent with US 69. Throughout Texas, US 69 is also referred to as Texas Forest Trail. US 69, US 96, and US 287 continue in a northwest, then west, route until its intersection with Interstate 10 in southern Beaumont. At this intersection, US 69, US 96, and US 287 merge with I-10. I-10/US 69/US 96/US 287 continue in a northerly direction through Beaumont for several miles. Just after the intersection with US 90, I-10 splits from the multiplex and resumes its easterly course, leaving US 69, US 96, and US 287 heading northwest through Beaumont. US 69 north of I-10 is also known officially known as Eastex Freeway, and is an official evacuation route, just as US 59 heading north from Houston is known as Eastex Freeway as well.

In Lumberton, US 96 splits from US 69 and US 287 and heads northeast towards Jasper, while US 69 and US 287 continue on a northwest path towards Woodville.

In Woodville, US 69 splits from US 287 a few blocks north of US 190. US 287 continues northwest towards Corrigan while US 69 proceed north towards Lufkin.

In Lufkin, US 69 is concurrent with US 59 and State Loop 287 while the route through the city is named Business US 69. US 69, State Loop 287, and US 59 continue around the east side of Lufkin until US 59 separates at the intersection with US 59 Business northeast of Lufkin. US 69 and State Loop 287 continue until the intersection of SH 103 and Business US 69 on the northwest section of Lufkin. At that point, US 69 is concurrent for a short distance with SH 103 and State Loop 287. At the intersection of US 69, State Loop 287 and SH 103, US 69 departs Lufkin and heads northwest while SH 103 and State Loop 287 head south.

US 69 continues on a north to northwest path through the towns of Alto, Rusk, Jacksonville and Bullard. Just south of Bullard, US 69 has a short concurrency with FM 2493. US 69 continues northward into Tyler.

In Tyler, US 69 continues northward through the city until the intersection of SH 110 and SH 155, where US 69 heads west and merges with SH 110 and SH 155 through Tyler. Around seven blocks from the intersection of US 69, SH 110, and SH 155, SH 155 separates from the concurrency and travels in a southwesterly direction, leaving US 69 and SH 110 traveling in a northwesterly direction. This continues until SH 110 separates from US 69 on the northwest side of Tyler. At this intersection, SH 110 heads west while US 69 continues north.

US 69 crosses Interstate 20 at Lindale where it is signed as "Main Street", before continuing north to northwest to Mineola and then on to a junction with Interstate 30 in Greenville. At the intersection with I-30, US 69 becomes concurrent with US 380 at its terminus. The concurrency continues around the southern and western sides of Greenville until the intersection with SH 224. At that intersection, US 380 heads west while US 69 continues north, then northwest, from Greenville to Leonard, where it encounters a brief concurrency with SH 78.

In Whitewright, SH 11 intersects and becomes concurrent with US 69 southeast of town. This continues until the intersection with SH 160, at which time SH 11 continues on a westward route and US 69 continues north through Whitewright.

US 69 continues north/northeast until Denison, where it merges with US 75 Business. US 69 and Business US 75 continue north until both intersect with US 75, at which time US-69 becomes concurrent with US 75. Both head northeast through the Oklahoma/Texas border.

US 69 and US 75 pass the Oklahoma border near the tiny town of Staley. They remain concurrent all the way to Atoka, where US 69 heads northeast and US 75 heads northwest. US 69 and US 75 briefly merge with SH-3 in Atoka but SH-3 remains concurrent with US 75 instead of US 69 when they split. In Stringtown, US 69 merges with SH-43. SH-43 splits from US 69 near the Ataka Reservoir and crosses it. US 69 passes right by the McAlester Ammunitions Depot. US 69 passes over Eufaula Lake 6 times. Near Muskogee, US 69 merges with US 64 and SH-2. At an intersection with US 62, US 64 heads west concurrent with US 62 while US 69 and SH-2 continue to head north. Near Vinita, US 69 and SH-2 interchange with Historic Route 66 and US-60. The two highways turn east and merge with HR-66 and US 60. In Downtown Vinita, SH-2 heads north while US 69, US 60 and HR-66 head east, passing I-44 a short while later. At SH-85, the three highways make an unexpected northward turn. The three highways merge with US 59 just south of I-44. Still south of I-44, US 60 heads northeast, paralleling I-44, while HR-66, US 69, and US 59 continue heading north, passing I-44. At SH-10, US 59 heads west concurrent with SH-10, while HR-66 and US 69 head north concurrent with SH-10. In Downtown Miami, SH-10 continues heading east, while HR-66 and US 69 turn northward. South of Picher and west of Quapaw, US 69 splits into US 69 and US 69 Alternate.

US 69 splits from HR-66 and heads north through the town of Picher. Just past the Oklahoma-Kansas state line, US 69 merges with SH-7. In Columbus, SH-7 continues heading north, while US 69 turns east and merges with US 160. US 69 and US 160 meet US 69 Alternate and US 400 near Crestline. SH-96 which continues east from this intersection, and then turns north and merges with all the highways. US 160 also turns north and merges with the four highways.

US 69 Alternate and HR-66 split from mainline US 69 south of Picher and west of Quapaw. US 69 Alternate and HR-66 head ENE through the towns of Quapaw and Baxter Springs. Just before Baxter Spring, US 69 Alternate and HR-66 pass into Kansas from Oklahoma. North of Baxter Springs, US 400 joins the concurrency. West of Riverton, HR-66 heads east, while US 69 and US 400 head north. North of Crestline, US 69 Alternate and US 400 meet US 69 and US 160 from the west and SH-96 from the east. US 69 and US 160 merge with US 69 Alternate and US 400. The concurrency of US 69, SH-96, US 400, and US 160 continues north.

While K-96 ends at K-103, US 69, US 400, and US 160 continue heading north. East of Cherokee, US 400 splits from the concurrency and heads west toward Cherokee. US 69 and US 160 continue heading north. North of Frontenac, US 160 splits from US 69 and heads east towards Lamar and Springfield, Missouri. US 69 continues heading north. South of Fort Scott, US 69 merges with K-7 again. In Fort Scott, US 54 merges with US 69 and K-7. The three highways continue heading north. North of town, US 54 and K-7 split from US 69 and head west; US 69 continues to head north. South of Pleasanton, US 69 merges with K-52. Northeast of Trading Point K-52 splits from US 69 and heads east. In the Kansas City suburbs, US 69 merges with I-35 and US 56/US 169. US 56, US 69, and US 169 split off from I-35 and heads east on Shawnee Mission Parkway. US 69 then heads north on Metcalf Avenue, rejoining I-35 and heading north. A short while later US 69 breaks off from I-35 and heads north on the 18th Street Expressway into Kansas City, Kansas. The highway then splits off and merges with I-70, US 24, and US 40 and heads east. At the intersection with US 169 at the 7th Street Trafficway, US-69 splits off and heads north. Just before reaching I-635, US 69 crosses into Missouri.

US 69 enters Riverside, MO,merges with I-635, and then almost immediately exits and merges with SH-9, heading east. A half-mile later, US 69 exits off from SH-9 and heads north. US-69 passes through Riverside, Northmoor, Gladstone, Claycomo, Pleasant Valley and parts of Kansas City proper before merging with I-35 for a second time, near Liberty. US 69 stays merged with I-35 for 7 miles (11 km) before it exits. After exiting the highway, US 69 immediately merges with SH-33 and heads northeast. At the B Hwy, in rural Liberty, SH-33 heads NNE and US 69 continues heading northeast. US 69 stays somewhat parallel to I-35 as it heads through Missouri, sometimes passing under it. West of Altamont, US 69 merges with SH-6. The highways turn north and a short while later SH-6 splits from US 69 and heads west, while US 69 continues heading north. Southwest of Bethany, US 69 merges with US 136 and heads east into Bethany. In downtown Bethany, US 136 heads east, while US 69 heads north. Still paralleling I-35, US 69 passes into Iowa from Missouri 22 miles (35 km) later.

In Lamoni, US 69 makes a sharp turn toward the east. West of Leon, US 69 merges with SH-2. In downtown Leon, US 69 heads north, while SH-2 heads east. East of Lake Ahquabi State Park, US 69 merges with US 65. The two highways continue to head north. At the intersection with SH-5, US 65 heads east concurrent SH-5 and US 69 continues to head north. In Ames, US 69 makes a left turn, then a right turn, and continues heading north. East of Clarion, US 69 briefly merges with SH-3. The two highways soon split with SH-3 heading east and US 69 heading north. Near Garner, US 69 briefly heads west concurrent with US 18, but soons splits off from it and heads north. North of Forest City, US 69 merges with SH-9 and continues heading north. SH-9 soon branches off to the west. Just south of Emmons, US 69 crosses into Minnesota.

US 69 enters the state at Emmons heading north-northeast through southern Minnesota. The highway terminates in Albert Lea at State Highway 13, formerly US 16.

When it was first commissioned in 1926, US 69 extended only from Leon, Iowa to Kansas City, Missouri. The part in Missouri had been Route 11 since 1922.

There was also a Business U.S. 69 in Fort Scott, Kansas (about 25 minutes north of the Frontenac, Kansas area), from about 1965 to 1990. Signs from the former Business Route still exist today; however, it no longer officially exists.