I've done this twice. Pittsburg to DC in 6 days. That seemed like rushing it as there is a lot to do along the trails.
First time with 3 others. We drove to Pittsburg. I found a hotel right next to the trail that let us leave the auto in their lot for free as long as we stayed at least 1 night. We stopped more often to sight see and do other things along the trail. A side trip to Falling Water for example. I did notice the trail grade a bit. Fenders are a must on the C&O. I learned it's better to ride through the puddles than to go around them. The bottom of the puddles is solid, the ground next to them is very mushy. I nearly went into the Potomac at one point trying to avoid a puddle. I rode a Gary Fisher mtb with 2" Kenda Komfort tires. Motels every night. That really cuts down on the gear to haul. We stayed extra days in DC as tourists. The one downside was we got to DC when congress was in session so everything is booked and packed with lobbyists, etc. We had to stay in a seedy place in Arlington. DC is a huge tourist destination as well at all times. We took Amtrak back to Pittsburg. The train arrives there at 12:30 AM! We had to box the bikes in DC. The walk on bike racks are booked many months in advance by the local commuters. The day we left DC, there was no baggage car so the bikes were shipped the next day via Amtrak to Colorado and back to Mt Pleasant Iowa before I could retrieve them about 5 days later. The prick running the Mt Pleasant station only works when the train is scheduled to arrive and if it's late, he locks the place up and leaves. No one to unload baggage so it just bounces between Denver and Chicago until a train is on time.
Second time I did the trails solo finishing up a cross USA ride. I had a slight tail wind all the time so I never noticed the grade going up. Hum, or maybe it was because I was in shape after riding 3000 miles. The grade map makes it look ominous but it isn't. No issues taking Amtrak from DC to Chicago.
I do recommend reserving motels a day in advance or more. One place I stayed at in Hancock should be condemned if it hasn't been already. The super 8 is a palace by comparison. The motel in Cumberland is excellent, right on the trail and elevators big enough for a couple bikes. All the motels were quite welcoming to cyclists. Bring good battery lights for the tunnels. The one is only rideable if you have very good skills and don't meet up with facing walkers or riders. It's the 3000 foot long PawPaw tunnel. A raised wood side walk in a tunnel that now houses a creek. Very damp and water constantly dripping down. Dissolved rock re solidified on the narrow surface makes it rather lumpy and slick at times. Be sure to bring a light rain jacket, better yet, one with a hoodie. Walking means you get even more cold water dripping down your neck. I met up with a tourist pushing her kids in a baby stroller in the middle of that tunnel, in heels and no lights. Yikes. I always take a battery headlight as a backup for the generator light anyhow. The rest of the tunnels are no problem. Big, airy, some are even lit.
This is a great pair of trails. I wouldn't mind riding them again. Long enough to be worth the travel time to get there and back. Much more interesting than the many rail trails in the middle of corn fields.