According to the HPL's abstract, this 1856 shot of the 300 block of Main is the oldest known photograph in the Houston Metropolitan Research Center archive. The caption goes on to say that this iteration of 300 Main was not long for the world. Fire soon claimed all of these wooden storefronts, which, by 1866, were replaced by these more substantial brick edifices.
Starting to look like a real city already...
Today, of course, the 300 block of Main looks like this:
And aside from Market Square it's the hoppin'est block in all downtown.