I assume you're asking about the usage in statements like "I guess he isn't here" and "I'm guessing he isn't here." The meanings are similar in these cases, and can often be interchangeable. The difference is pretty subtle.
When you say "I guess he isn't here," it implies that you are drawing a conclusion based on your observations. "I've looked everywhere, and I can't find him. I guess he isn't here." You could replace "I guess" with "it seems like..." or "the only answer seems to be that..."
When you say "I'm guessing he isn't here," the statement sounds a bit less conclusive. It sounds like you're saying that this is what you assume, but there's still a sense that you're waiting for further confirmation. This phrasing is often used as a question. "I didn't see him when I came in. I'm guessing he isn't here?" You're making a guess, but you still want to know whether or not your guess is correct.
If you go out for lunch with a friend, and your friend orders a vegetarian meal, you could say, "I guess you don't eat meat." This would be more of a statement of a fact: you are making a guess that the person doesn't eat meat. You could also say, "I'm guessing you don't eat meat." This is more of an invitation for the other person to respond, so your friend can tell you whether or not it's true that he/she doesn't eat meat.
Like I said, though, the two uses are pretty interchangeable, and sometimes the tone of the statement is more important than which word you choose. I don't think you need to worry too much about the difference. Both phrases mean that the speaker is making a guess about something.