I'm sure there have been very similar questions posed here, however - The final chord in most songs is the key, or root chord. This needs to be established first. As Shev. says, the bass will often play that root note, so it becomes easy to find.
It will also tell if a song's in major or minor. Having found that, by matching it with a chord played on an instrument simultaneously, a set of chords to complement that will be necessary. Working from the major perspective, I,ii,iii,IV,V,vi will be the list to take chords from. As in Cmaj., say. C, Dm, Em, F, G, Am will be the most commonly used chords. The first 'main' chord will often be the key chord, too. So, if it is, then the next chord, if also major, will be a 50/50 between F or G. If the progression moves to a minor, there's a 33% chance of just guessing. Not bad odds either way!
I feel this is maybe easier to do whilst listening to the song, rather than taking a random key and trying to play the song in that key - unless, of course, one only knows a few chords that fit in a key.
Start with simple songs - Happy B'day, Jambalaya are a couple. Bear in mind that usually the two most prevalent chords are I and V - two chord songs generally only use those.
Key signature is really a different issue - you maybe just meant key?