In the U.S. state of Vermont, U.S. Route 4 (US 4) extends for 66.06 miles (106.31 km) between the New York state line at Fair Haven and the New Hampshire state line at White River Junction. It is one of the main arteries between New York and New Hampshire.

Upon crossing into Vermont from New York, US 4 immediately expands from a two-lane highway to a four-lane expressway. US 4 changes from being signed north–south (in New York) to being signed east–west (in Vermont). The historic routing of US 4 runs nearby as VT 4A, which later becomes US 4 Business as it enters the town of Rutland.

The 19-mile (31 km) US 4 expressway was built in anticipation of the proposed, but never built, East-West Highway which was supposed to link the population centers of northern New England. As such, this section of freeway meets Interstate Highway standards. The freeway has junctions with VT 22A in Fair Haven and VT 30 in Castleton. In West Rutland, the last numbered exit on the highway, exit 6, leads to US 4 Business, which provides access to the town centers of West Rutland and Rutland town. The expressway veers south just outside the limits of Rutland city, ending at an at-grade intersection with US 7 south of the city.

US 4 overlaps with US 7 north into downtown Rutland, meeting the east end of its business route along the way. US 4 then leaves US 7 along Woodstock Avenue as it heads northeast out of the city. East of Rutland city, US 4 is a two-lane highway, meandering through the Green Mountains, passing by the town center of Mendon towards the town of Killington. In Killington, US 4 joins VT 100 as they pass through Killington center along the Ottauquechee River valley until the village of West Bridgewater at the Bridgewater town line. VT 100 splits off to the south while US 4 continues following the Ottauquechee River east through Bridgewater center into the town of Woodstock. Several miles later, US 4 enters the incorporated village of Woodstock, where it meets VT 12 and VT 106. Southbound VT 12 and eastbound US 4 overlap for about 4 miles (6.4 km) along the river and split at the village of Taftsville, in the northwest corner of the town of Hartland.

US 4 continues following the Ottauquechee River into the town of Hartford, passing by Quechee Gorge State Park and circling around Deweys Pond heading north to the south bank of the White River. Here, US 4 has an interchange with Interstate 89, then turns eastward following the river bank into the village of White River Junction. In the village, US 4 joins US 5 as they cross the White River. At a four-way intersection immediately after the crossing, US 5 continues north, VT 14 begins to the west, and US 4 continues to the east. US 4 crosses the New Hampshire state line at the Connecticut River after a quarter of a mile.

The road running from the New York state line (towards Whitehall, New York) at Fair Haven eastward through Rutland and Woodstock to White River Junction was designated as Route 13 of the New England road marking system in 1922. In late 1926, New England Route 13 was incorporated into the newly established U.S. Highway System as US 4. In the 1960s, construction of the 19-mile (31 km) expressway section of US 4 began.[citation needed] The middle segment of the expressway from exit 5 in Castleton to exit 6 in West Rutland opened to traffic in 1969. Two years later, the western segment from the New York line in Fair Haven to exit 5 also opened. The original surface alignment of US 4 was re-designated as VT 4A. The construction of the eastern segment (from exit 6 to the intersection with US 7) was delayed for several years and did not open to traffic until 1986. The original surface alignment east of exit 6 was redesignated as US 4 Business.

U.S. Route 4 Business (US 4 Business) is a 4.371-mile (7.034 km) alternate route of US 4 serving the city of Rutland and running north of US 4. It begins at exit 6 of the US 4 expressway in West Rutland and heads north to Main Street in West Rutland center, where it meets the east end of VT 4A. US 4 Business turns east, following Main Street into the town of Rutland. In Rutland town, the road changes names to Rutland Road and intersects with VT 3 at the town center. About 0.3 miles (0.48 km) later, the road enters the city of Rutland, becoming West Street. US 4 Business briefly shifts north one block to use State Street before returning to West Street after half a mile. The route ends at an intersection with US 4 and US 7 in the center of the city.