Great barbecue can be had all over the place in the Southland (and many places up North, too, for that matter), and while it might be good sport to argue about it, the fact is that it's really easy to find and a delight to eat. My best (objective) suggestion is to never mind all the reviews and the claims to fame, but simply find some likely-looking locals and approach them with something friendly like "hey, Bubba, where y'all reckon the best barbecue pork pig around here is?" and follow their advice. Or if you don't care for the Bubba stereotype, say something similar but try "Hey, Cooter" instead. Or if the person is not Caucasian, use some degree of political correctness, as your own good judgment dictates. .... In any case, the real enjoyment of the barbecue odyssey you propose is the discovery, on your own, of many of these widely scattered and amusingly diverse establishments all along the way. .... Do keep in mind, though, that white bread is the proper accompaniment, and sweet tea if you can stand it.

My husband recently went to San Antonio and had to go into Austin for good BBQ. He liked the Ironworks but loved The Salt Lick (in Driftwood just outside of Austin) so much, he went back a second time, and even brought home a set of their bottled sauces. We always search for great BBQ whenever we are on the road in the south.
So far, our favorite BBQ that we've had is in Buckhead in Atlanta called Fat Matt's.

Mobile, AL is on the direct route and has many local specialty seafood/cajun restaurants. The Grand Hotel is a Civil War vintage famous destination. Gulf Shores, AL immediately East has the Floribama, a redneck landmark. The Florida panhandle has a great fishing village, Appalachicola with several local flavor destinations. Destin and Fort Walton Beach are great Gulf Coast stops.

Oh thank goodness someone mentioned the Salt Lick. You must go to the Salt Lick for bbq if you are near Austin (go to the original in Driftwood, not the one in Austin). Have family style - all you can eat brisket, sausage, ribs, cole slaw, potato salad and beans. BYOB for alcohol (yes, just bring in your cooler of beer). And polish it off with cobbler. Yum.

http://www.saltlickbbq.com/

Don't forget about Dreamland if you come through Tuscaloosa, Alabama, perchance. And if you're driving north to Memphis from New Orleans you need to stop in Hattiesburg, Mississippi, for some of Miss Leatha's barbecue. It's the real thing. Anyone in town can tell you how to find it.

This is making me hungry! I too ate at the GA Pig one time on a road trip and it was fantastic BBQ! I looked for it several years later and didn't see signs...hope I just missed it and that it isn't gone!

I too am a big fan of Dreamland in Tuscaloosa!

I am a vegetarian but after living in Austin for four years even I know that the Salt Lick is the best. (I always passed on invites to head out there because the only thing that doesn't have meat in it is the wonder bread.) Glad to see others agree!

eatin' good in the neighborhood! This one really put a smile on my face, Joanna. Great memories of my road-trips with the blues'n'BBQ boys. I was reminded of my Texas BBQ trip when I visited Mo's in Pismo Beach - check out his BBQ tour! http://www.mosbbq.com/about.htm

When I did my last circuit Billy Blues was still in San Antonio - now it's a happenin' burger joint (Sam's Burger Joint) with music - but I think there's still one in Houston. In Austin, we always eat at the Ironworks - tho' the locals probably know a better place. We dug the brisket at Keno's in New Braunfels - and it's on the way to Austin. Good news is you can eat 3-4 meals a day!

You're headed to the wrong part of the country for BBQ -- should have come throught the Carolinas! (well another trip, perhaps!) There are always competitions here pitting Eastern Carolina style vs Western Carolina style. It's all fantastic to me :-)

In Houston, we like Pappas BBQ, Goode Co., and Otto's. Highly recommend getting brisket in Texas, links are good too!

I just wanted to thank everyone so much for all the great information.
and give a little explanation for our itinerary. honestly, i dont remember how i decided to start with san antonio, but now that i have read all about it i really want to go. and i have always wanted to go to savannah. and thats really all the explaining i can do. the bbq part got added later because we love to eat bbq, but we are also hoping to see the south.
so now, here is the basic itinerary. we know theres alot of driving in a small amount of time, but we'll get to see alot.
san antonio
to austin to houston
to new orleans
to mobile to tuscaloosa
to atlanta
to savannah
to charleston
keep the suggestions coming! i'm writing them all down and appreciate them all.
sorry north carolina and tennessee, we'll visit you another time :0)

If you can afford it, stay on the River Walk in San Antonio. If not, be sure to get yourself down there and enjoy the vibe. Wonderful place.

In Savannah, try Johnny Harris
In Mariette, Ga. a suburb just north of Atlanta, try Swallow in the Hollow.

Both are excellent

If you get hungry between driving from Dreamland in Tuscaloosa to Mobile, AL on I-65, stop in the PEACH PARK on I-65 Exit 205 for a BBQ sandwich - very generous portions - end the meal with a seving of peach cobbler or frozen vanilla yogurt topped with their fresh chopped fruit bar - to die for!

Check out the Brick Pit on the west side of Mobile.

If you can work it in, the big names in North Carolina barbecue, all not too far off I-85, include:

Lexington Barbecue (in Lexington)
Stamey's (in Greensboro)
Bullocks (in Durham)

and then if you take I-40 to I-95 you can hit Bill Ellis in Wilson.

In Columbia, SC, hit Maurice's for mustard-based SC-style sauce.

Not barbecue, but classic good road food to be had in Atlanta at the Varsity and at the Beacon Drive-In in
Spartanburg, SC.

Check out RoadFood.com

Joanna,
There is a Dreamland in Montgomery, also. You could cut a few hours off your trip by going from Mobile to Atlanta via Montgomery, unless you have another reason for going to Tuscaloosa. Jim & Nicks BarBQ is also in Montgomery. On I-85, south of Atlanta, Newnan, Ga has Sprayberry's which has been family owned for over 75 yrs. Sounds like an awesome trip! Enjoy.

In Houston, Goode BBQ (or Seafood, or Mexican Food) are great. Jim Goode is the real deal, has been featured by Emeril several times as one of the best BBQ joints in America. Near Rice University and The Galleria area. Worth the trip. Honky-tonk next door, stand in line for food then eat on picnic tables. Try the turkey or "dirty" rice for a change of pace.

Read all the posts, great advice. BBQ is certainly different depending on the region you're in. Many of these suggestions are fantastic, so enjoy!
My personal favorite, though not on your route this trip is a place called Joe's Real BBQ in Gilbert, Arizona. It is real good, and I lived in Texas for over 10 years, so I've had some great BBQ. They smoke their meat over pecan wood, and their sauce is like no other I've ever tried.
If you get to the Phoenix area, head towards Gilbert. I think they have a website, too.

DancingBear left out Wilber's and Scott's in Goldsboro--maybe the most famous in NC.