Are you talking by car? Or by bike?
I've gone to St Marys by car before and I did I79 -> I70 -> WV2. (Google recoomends crossing to Ohio, taking OH 7, then crossing again at St M)
On a bike, I thing your route would work.
Here's a Road route I'd consider.
1) Use Oscar Swan's Potato Run Rt to get west of the city
(West end circle -> Steubens treet. Up and over Baldwin Rd to Campbell run. Right on campbell Run up to 22-30. Left on the shoulder of 22-30 for 1/4 mile or so - it's ridable - to the exit for Old Steubenville Pike. Stuebenville Pike to Robinson Hwy, AKA PA 980, AKA PA Bike Rt A, make a left to follow it south. Swans' Potato Run makes a right here.)
2) Stay on PA Bike Route A until you get to Waynesburg
ftp://ftp.dot.state.pa.us/public/pdf/bikes/state_mapA.pdf
3) From Waynesburg, take PA 18 (haven't ridden it, but it is famously good for bikes) South to the WV border where it becomes WV 69.
4) Somewhere around a town in WV called "Hundred," 69 Joins up with WV 7. Take that to WV 2 and go south to St Marys.
I'd take several good maps of SW PA and northern WV with you. I'm not sure how many trucks you's have to deal with on any of these roads, but I'd be concerned about WV 2 - lots of industrial plants along the river and big trucks.
Or, a Rail-Trail heavy Route.
http://www.wvrtc.org/trails/index.html
Get to Point Marion, PA, Dirt Road south along the railroad track and the Mon to the WV North Mon trail. Follow the Mon trail to Fairmont, then the North Fork *River* Trail (different rail from the North Fork Trail.) to Shinnston.(about 30-35 miles on the trails)
Roads from Shinnston to Wolf Summit/Bristol (probably WV 20, Bean Run Rd, and Old US 50) then take the North Bend Trail about 20 more miles to Ellenboro
Then take WV 16 north-west to St Marys.
There might also be a way to use the Panbhandle trail west, then head south.
Mick