When it became apparent that the automobile was a viable way of transportation of both people and goods across the county, the federal government decided it would be worthwhile to have roads that cross state lines for continuity. Unlike state routes which could be numbered however the state pleased, the US Highway System dictated that roads had to be numbered from east to west, north to south. For example, US Route 1 runs from the US-Canada border in Maine, to the Florida Keys in Florida while US Route 99 ran from the Canadian border in Washington to the Mexican border in California.
These roads were also allowed to have auxiliary and bypass routes. These were to be numbered with three digits, while their main parents were only allowed to have two digit numbers. Three digit routes had very little regulation, other then there could only be a maximum of nine auxiliary routes per parent and the first number was assigned in the same way as the major routes (east to west, north to south). This was due to the fact that auxiliary routes were allowed to traverse over state lines. There was one major exception to the three digit rule, US 101. Another border to border route, it was not thought to be added to the system until US 99 had already been signed. AASHTO was able to bend it's own rules and say that the first two digits counted as one number, ten. That would technically make is US 10-1, but for simplicity, it's just US 101.
These roads were also allowed to have auxiliary and bypass routes. These were to be numbered with three digits, while their main parents were only allowed to have two digit numbers. Three digit routes had very little regulation, other then there could only be a maximum of nine auxiliary routes per parent and the first number was assigned in the same way as the major routes (east to west, north to south). This was due to the fact that auxiliary routes were allowed to traverse over state lines. There was one major exception to the three digit rule, US 101. Another border to border route, it was not thought to be added to the system until US 99 had already been signed. AASHTO was able to bend it's own rules and say that the first two digits counted as one number, ten. That would technically make is US 10-1, but for simplicity, it's just US 101.
A lot of US Highways were supplemented, or in some cases replaced by, the Interstate System in the 1950's and 1960's.