Write a great story. Many people are so eager to be a published author that they rush their story onto paper and submit the first draft. Even the best writers go through several drafts before producing a story worthy of publication. Get feedback from people you trust.
Write a compelling query letter and a succinct synopsis. Few agents, editors or publishers will accept your 1,000-page tome right off the bat. A one-page query letter introduces you, your story and your qualifications. A two- to four-page synopsis outlines your book, complete with the ending. Do not end with a cliffhanger hoping to intrigue the agent or publisher.
Get a literary agent. Agents have a direct pipeline to publishing house editors and will handle contracts and negotiations for you. Few publishers will accept unsolicited manuscripts. Research agents on the Internet or in the most recent Guide to Literary Agents, Guide To Book Publishers, Editors, & Literary Agents or the Association of Authors' Representatives website (see Resources below). Seek an agent who represents other authors in your genre.
Submit a typo-free manuscript to the agent. Proofread your manuscript again and follow standard manuscript formatting (see Resources). Also heed the agent's submission guidelines. Include a self-addressed stamped envelope for their reply.
Self-publish your book. This, of course, means paying for publishing and doing your own publicity and marketing, but the upside is that you can call yourself a published author for your next book's query.
Don't give up. Work on your next book while continuing to submit your first one to other agents or publishers. Do not take rejections personally.