At this point, it becomes a four-lane surface road until it reaches western Bexar County where it becomes a freeway, joining I-10 in Downtown San Antonio.

In eastern Houston, US 90 splits from I-10 and heads northeast towards Liberty, eventually traveling through downtown Beaumont where it rejoins I-10 for the rest of its routing through Texas.

Beginning at Seguin, US 90 Alternate splits from US 90 and travels parallel to the south, rejoining the main route in northeast Houston.

In Lafayette, US 90 and I-10 part ways: I-10 proceeds east to Baton Rouge, while US 90 takes a southern turn and passes through New Iberia, Franklin, Morgan City, and the Houma – Bayou Cane – Thibodaux metropolitan area before reaching New Orleans.

The four-laning of US 90 was pushed in the 1990s by former State Senator Carl W. Bauer through his role as the chairman of the Governor's Interstate 49 Task Force while also a member of the Greater Lafayette Chamber of Commerce.

Prior to Hurricane Katrina, Mississippi's portion of US 90 was entirely four-lanes except for a very short segment at the state's west end leading to the old Pearl River Bridge into Louisiana.

That segment of old highway is obviated for most purposes by an extension of the four-lane roadway from its split with US 90 to I-10 just east of the much newer Pearl Bridge.

Before Hurricane Camille in 1969, the 26-mile (42 km) stretch of US 90 from the Bay St. Louis Bridge at the west end to the Biloxi Bay Bridge at the east was one of the most scenic roadways in the south, offering beautiful views of the Gulf of Mexico on its south side and lovely mansions — some antebellum — on its north.

'US Highway 90 Project History' recounts in some detail this roadway's colorful past in Mississippi, dating back to the early 20th century when it was part of the Old Spanish Trail.

In Gadsden County, US 90 cuts to the southeast toward downtown Tallahassee, where it passes the north entrance of Florida State University and expands to six lanes until its intersection with US 27.

Continuing east, the highway is a two-lane road north of I-10 along the rest of its route, except as it turns to the south to pass through Lake City at I-75.

The Crescent City Connection bridge over the Mississippi River in Sector 49, also known as US 90 Business, remained intact and was the only usable route out of that city in the immediate aftermath of the storm until the section of Leake Avenue/River Road between New Orleans and Metairie was able to be cleared of heavy debris, but was blocked off by Jefferson Parish and Gretna law enforcement officials in a politically controversial move to prevent the looting and general anarchy from spreading to the relatively intact west bank of the Mississippi River.

Two-way traffic resumed on the eastbound lanes of the bridge on May 17, 2007, after an afternoon ceremony,[7] effectively ending the temporary ferry service.

To many area residents' and leaders' delight, the bridge's westbound lanes opened to two-way traffic after a ceremony and parade on November 1, 2007, two weeks ahead of schedule.

[10] After it was closed due to storm damage, the 1929 vintage bridge carrying US 90 over Chef Menteur Pass was repaired and opened to traffic on August 11, 2006.