Publishing houses almost always want submissions to come from literary agents and not directly from writers. However, there are exceptions. In the Science Fiction/Fantasy or Romance world, one can still find a few publishers willing to accept unsolicited manuscripts.

Agents know how to query the right editors, firsts testing the waters to see if a manuscript is a potential fit. If the agent gets a response to the initial inquiry, usually only then will he or she send the full manuscript for consideration. Agents often have established relationships with editors at publishing houses. They are familiar with an editor’s tastes, quirks, and interests.

It’s best for a writer—especially a brand new one—to seek out a literary agent. The pro not only will know the right editors to approach but just how to describe your project.
Convincing an agent to handle your work is no easy task. Be prepared to send many queries—25 or more—before you land the right representation.
Of course, if you are best friends with someone like John Grisham and are writing in his category, you could ask him to introduce you to his editor. Even if the editor agrees to take a look at your work, if they are interested they will want you to seek an agent to orchestrate the book deal.

Keep writing.