This is on a 2002 excursion. Should the inner fender be removed first?

 

First Id remove the tire, then the inner fender. Removing the tire will give you a lot more room to work.

 

if you are worried about working room and are trying to work on the manifold/up pipe joint but the bolts are rusted try this out:
http://the-hush.com/
it hooks over the manifolds ears and you can reattach the flange to it rather than the old/corroded bolts. Its much easier to install than trying to retap or remove the old bolts yourself.