Main Street is (not surprisingly) the main street of Woodland. Along with West Main Street and East Main Street, it forms the main east-west thoroughfare through downtown Woodland and is where most of the shops and restaurants in town are located. It overlaps with the route of County Road 22 where that road passes through Woodland. As such, it is situated exactly one mile south of Kentucky Avenue (which overlaps with the route of County Road 20) and exactly one mile north of Gibson Road (which overlaps with the route of County Road 24).

Main Street becomes West Main Street west of West Street and becomes East Main Street east of East Street.

Note: If looking for an address, there is a difference between West Main Street, Main Street, and East Main Street. As with pretty much all the other streets in town that have "East," "West" or "North" appended to their names for portions of their lengths, the house numbers or building numbers get reused when the street name changes. Address numbers on Main Street and other such streets generally count upward as they move away from West Street in either direction. They also count upward as they move away from Beamer Street in either direction. Address numbers typically continue counting upward as they cross East Street, despite the change of street names at that point.

Between County Road 98 and the Main Street exit on Interstate 5, West Main Street, Main Street, and East Main Street all form part of the I-5 Business Loop. Note: The Main Street exit on I-5 actually leads to and from East Main Street., not Main Street. But the signs on I-5 say "Main Street."

West of County Road 98, West Main Street becomes Highway 16 and also County Road 22.

East of County Road 103, East Main Street becomes County Road 22 again.

West Main Street

West Main Street runs between County Road 98 and West Street. It intersects Ashley Avenue, Cottonwood Street, Community Lane (which heads south only from West Main Street), and California Street. Along the way, it passes by the Westgate Shopping Center (including Raley's, JOANN Fabric and Crafts, Sol Mexican Cuisine, Country Waffles, TOGO's Sandwiches, L & L Hawaiian Barbecue, and Woodland True Value Home Center), Cantina Los Primos Tacos y Cerveza, Foy's Bike Shop, ARCO/ampm, Judy's Burger & Grinder, Rite Aid, Starbucks, Yolo County Parks & Resource, the Woodland Thrift Center, Subway, the West Main Plaza (including La Pasadita and Wienerschnitzel), Carl's Jr., KFC, Walgreens, and Mariscos el Viejon.

West Main Street has been planted with a few street trees by the city, on its far west end, in front of Raley's. The trees are Chinese Pistache (Pistacia chinensis) and unidentified pine trees.

Main Street

Main Street runs between West Street and East Street. It intersects Grand Avenue (south only), Academy Lane (south only), Cleveland Street, Walnut Street, Elm Street, College Street, 1st Street, 2nd Street (south only), 3rd Street, 4th Street (heading south), 4th Street (heading north), 5th Street (south only), 6th Street (heading south), and 6th Street (heading north). Along the way, it passes by Purity Plaza (including Wingstop, Rafael's, Pupusería la Chicana, and Dutch Bros Coffee), Falling Prices Woodland, The Crazy Bakery, Pete's Restaurant and Brewhouse, MAX TASTE Lahorian Grill, Nugget Markets, Sola Bee, the State Theatre & Multiplex, El Charro Mexican, Timothy's Bakery, Father Paddy's Pub, Bangkok Cuisine, Las Brasas, Main Street Lounge, The Burger Saloon, Morgan's on Main, Savory Café, Thai Pepper, La Fogata, and the Superior Court of California, County of Yolo Courthouse.

Main Street has been planted with street trees east of Cleveland Street. The street trees include three invasive weed species: Canary Island Date Palm (Phoenix canariensis), Purple-leaf Plum/Cherry Plum (Prunus cerasifera), and Black Locust (Robinia pseudoacacia 'Purple Robe'). However, Western Hackberry (Celtis reticulata) is also planted as a street tree on Main Street and is native to California, though it is not native to Woodland. Other non-native street trees on Main Street include Trident Maple (Acer buergerianum), Red Maple (Acer rubrum), European Hornbeam (Carpinus betulus 'Fastigiata'), Common Hackberry (Celtis occidentalis), Chinese Hackberry (Celtis sinensis), Crape Myrtle (Lagerstroemia indica), Japanese Crabapple (Malus floribunda), Black Tupelo/Sour Gum (Nyssa sylvatica), Medjool Date Palm (Phoenix dactylifera), Chinese Pistache (Pistacia chinensis), Scarlet Oak (Quercus coccinea), Northern Red Oak (Quercus rubra), Little-leaf Linden (Tilia cordata), and Saw-leaf Zelkova (Zelkova serrata).

East Main Street

East Main Street runs between East Street and County Road 103. It intersects Johnston Street (south only), Thomas Street (south only), E Street (north only), Matmor Road (south only), and Industrial Way (north only), is an exit on Highway 113, intersects Pioneer Avenue, is an exit on Interstate 5, and then intersects Hazel Court (south only), Yolo Polo Plaza (south only), Douglas Lane (south only), County Road 102, Freeway Drive (south only), Quality Circle (south only), and Hanson Way. Along the way, it passes by 7-Eleven, Jack in the Box, Woodland Crossroads Shopping Center (including Ace Hardware, Grocery Outlet, Harbor Freight Tools, Ross Dress for Less, Tractor Supply Co., Sherwin-Williams Paint Store, The Habit Burger Grill (Drive-Thru), and Dutch Bros Coffee), Quik Stop, Woodland Taco Truck, Denny's, Sonic Drive-In, Chevron, Starbucks, Walmart, Tacos la Flamita de Oaxaca de Viernes a Domingo, Goodwill Sacramento Valley & Northern Nevada, GameStop, The Home Depot, Burger King, and another Jack in the Box.

East Main Street has been planted with street trees east of E Street. The street trees include two species that are native to Woodland: Western Sycamore (Platanus racemosa) and Blue Oak (Quercus douglasii). Additionally, Coast Redwood (Sequoia sempervirens) is planted on East Main Street and is native to other parts of California. Non-native street trees on East Main Street include Deodar Cedar (Cedrus deodara), Crape Myrtle (Lagerstroemia indica), Tulip Tree (Liriodendron tulipifera), Southern Magnolia (Magnolia grandiflora 'St Mary'), Chinese Pistache (Pistacia chinensis), London Plane (Platanus × hispanica), and Holly Oak (Quercus ilex).