Currently the longest single-state mileage of any US route is 893 miles (US 83 in Texas).  Historically, before US 101 was truncated to Los Angeles, that route was undoubtedly the record-holder: the California segment of US 101 was about 941 miles (give or take a few, depending on which year, since the alignment changed many times and in many places). 

Historic US 99 in California was the second-longest route through a single state, although its mileage is even more difficult to measure, since it was replaced by I-5 in many areas, and as a result some segments of the original route have been vacated.  The Historic Highway 99 Association of California offers a length of 917 miles.  Although that page does not specify a year, I am sure that figure is reliable, since my own back-of-the-envelope calculation yielded a similar distance.  (Note that drivers choosing US 99E between Sacramento and Red Bluff had to travel 2.2 miles further than those who chose US 99W.)

Thanks to this blog post, I recently became aware of "the Palm and the Pine" along what is now CA state hwy. 99, just southeast of Madera.  In the median of the highway, a palm tree and a pine tree are planted side by side (one representing southern California, and the other representing northern California):

US 96, US 14, US 75, US 99, US 240, US 42, US 138, US 360, US 431, US 380, San Antonio NM, Astoria, US 650, US 28, US 113, Crescent Jct, San Angelo, Long Beach, US 270, US 412, US 277, Springer, Trinidad, US 41, US 99, US 130, US 209, Toledo, Cleveland, Cumberland Gap, Cincinnati, US 91, US 75, US 175, US 80, Louisville, US 601, US 167, US 111, US 97 ​

The other day I was driving north on C-470, and I wanted to go east on the 6th Avenue Freeway towards downtown Denver.  That movement is shown on the map below:

I rarely drive that direction along C-470, but I have lived in Denver for a long time, and I'm pretty confident about knowing my way around.  So as I approached, I was quite certain that I would need to follow eastbound I-70, and that the exit for eastbound US 6 would come up shortly after that. 

​But then I saw this: the first sign that references US 6 on northbound C-470:

The photo below was taken looking east along the international boundary between Canada (to the left) and the U.S. (right).  The large structure (with the flags on top) is the Peace Arch, which straddles the border.  (It is not square to the boundary line; rather it is situated at a slight diagonal that roughly matches the angle of the roads that run through here.)  If you look closely, you can see three boundary obelisks in the foreground:

I am about to ask a simple question.  It is not a trick question, so no reason to over-think it.  The map below (like most maps) is oriented with north at the top.  You might not be able to make out much detail, but that's ok, because all I want you to do is take a look at the highway shown in blue.  And the question is simply this: does this highway run north-south?  Or does it run east-west?

US 87 and US 287 converge in Dumas, Texas, and share about 49 miles of pavement down to Amarillo, where the two routes separate again.  ​

(Most recently updated 7/30/2021)  One of San Angelo's marketing slogans is "The Oasis of West Texas".  This is not hyperbole; most approaches to the city are somewhat stark, so in contrast upon arrival in Angelo, one may well be pleasantly surprised at all of the rivers, reservoirs, trees and other vegetation:

One of the city's other monikers is "The Pearl of the Conchos", which has a double meaning, referring to the freshwater Concho pearls that were historically harvested from area waterways.  The three branches of the Concho River all converge in San Angelo; here is another slogan from days gone by:

When the US highway system was inaugurated in late 1926, the only US route to initially serve San Angelo was US 385 (that is, the original US 385, not the current US 385).  The new designation was added to Texas State Highway 9:

US 322, Tampa, US 67, US 522, US 31, US 51, US 176, US 44, US 113, Milwaukee, Original US 46 proposal, US 34, US 15, US 1, Minnesota rogue routes, US 301, Miami, Hardeeville, Walterboro, Fox Valley, Richmond, St. John IN, US 36, US 18, US 83, US 183, US 275, US 385, Rapid City, US 92, US 129, US 175, US 276, US 310, US 411[i], US 121[i], US 117[i], Wilson, Wilmington NC ​

When the US route system was conceived in the mid-1920s, one of the guidelines was that the longer, more important routes would be assigned 1- and 2-digit numbers.  Given that, US 46 really seems like an outlier.  At only 75 miles in length, it is the shortest of all 1- and 2-digit US routes.  Not only that, but US 46 is entirely in one state (New Jersey).  Why would AASHO consider a short, single-state highway to be worthy of a 2-digit US route designation?  Historic documents in their route numbering archive reveal at least some of the answers.  As it turns out, when US 46 was first proposed in the mid-1930s, it was envisioned as a route running between New York City and Cleveland, along the corridor shown on this map: