With computers making it so much easier to produce a manuscript, more people are finally writing that novel that's inside them. This means there are a lot more books for editors to read and choose between. Editors may receive books three ways: directly from one of their authors, from an agent or as unsolicited. Moreover, unsolicited manuscripts normally pass through a slush pile where a first reader decides whether the manuscript should be passed on to an editor.
Major Publishing Houses
Unfortunately, while book writing has increased in volume, book buying hasn't. Many publishers are printing fewer new titles each year, meaning they buy fewer new titles. Since publishing houses already have a stable of authors and they offer fewer publishing slots, there are fewer still slots to try out on new authors. Yet the volume of new author submissions continues to grow. This, along with general industry downsizing, has contributed to many publishing houses doing away with slush piles. So few major houses accept unsolicited manuscripts. Though most publishing houses have websites, the best source for information on which houses (or specifically which editors at the houses) accept an unsolicited manuscript is found in books. At the library or book stores, find the market place books on publishing.
Independent publishers are smaller presses. While they lack the distribution of the major houses, many of them have distribution in major chains like Barnes and Noble. Small presses rely on sales through the Internet, via their own website or through sites like Amazon. Some small presses sell books at conventions. Since there is a rising demand among new authors to sell their manuscripts, and a decreasing supply of new books from the major houses, the small presses have stepped in to fill the void. And most small presses accept unsolicited manuscripts. While working with a small press means a much smaller print run and much smaller earnings, it can establish a publishing background that may improve the chances of getting an agent.
Get an Agent
These days, even many agents won't accept an unsolicited manuscript, requiring that you first query and pique their interest. An agent is unlikely to represent a new author with only a book proposal. New authors have to demonstrate the ability to write. While a sample chapter will do that, new authors also have to demonstrate the ability to finish a project. So, have a finished manuscript and write a compelling query letter.
Follow all Formats & Guidelines
Having a finished manuscript is of little value if it is not in the proper format. Standard formatting is easily found in books on manuscript submission. In general, keep the manuscript plain and simple, as if it came off an old fashioned typewriter. Making a manuscript "stand out" generally says "rank amateur." If the manuscript doesn't look professional, it won't get read, and so your story, no matter how brilliant, won't be discovered. Guidelines for a specific publisher are generally available on line, if the house accepts unsolicited manuscripts. If you mail a SASE and request a copy of guidelines, most houses will oblige. Guidelines are invaluable tools.
If your manuscript is not picked up by a publisher or an agent, consider other options. Hopefully, you received some feedback (most likely from an agent) regarding why your manuscript was not picked up. Perhaps the manuscript would benefit from a book doctor. Some book doctors do extensive rewriting while others provide a critique, pointing out what needs fixing. Another option is self-publishing, requiring your own financial investment as well as distribution. Be aware that most success stories dealing with self-published books have dealt with self-published non-fiction books. Self-publishing houses always accept unsolicited manuscripts.