I've done it several times, usually in my pickup or full-size van, but once with 30-foot C. I'm always going south on 59 (my northbound routes are different, it is a time of day thing) so can't advise on connections northbound.
The route through Atchison is not too bad. I've side tripped a couple of times there to visit the Amelia Earhart Birthplace museum, which is not too bad with a smaller vehicle, but you can get trapped in that neighborhood with a RV.
South side of St Joseph can be slow going, particularly the Lake Avenue section, which is a busy residential-light industrial section with narrow old rough streets and diagonal three-way to five-way intersections.
Once you get on US-36 it is four-lane divided (but not controlled access) all the way to the Mississippi River, with traffic lights only in Cameron around the I-35 junction.
Be sure to check with DOT in Kansas and Missouri. I've been caught a couple of times by road closings between Atchison and St Joe, and forced to do some backtracking.
Tom Test
Itasca Spirit 29B