I have a 1959 F-250 with a 223. I am wondering if I can bolt a 300 inline 6 right to the 4 speed stock manual tranny that is in the truck?

 

Nope, Nada, Neyt!
Bolt Patterns are completely different for the 223c.i.er & 300c.i.er, so the Original Tranny bolt patterns for your '59 will Not aligne w/ the 300c.i.er bolt patterns.
If you wish to Up-date to a 300c.i.er, you're going to have to Up-date to a Matching Manual or Auto Tranny as well w/ the correct Bellhousing for the 289/300/302/351 Matching Tranny Bolt Patterns.
Why on earth would you wish to mate an Engine & Tranny that are a decade apart in design from each other & that are completely mismatched for one another? Besides, it's like finding a Needle in a haystack these days to Find a Mechanic that knows how to work on the Older designed Trannies anymore, let alone finding a ready supply of parts for them.
Installing a 300c.i.er will require you to either Punch-out the Radiator & Move it foreward or set the Engine back almost against the Firewall so that the it'll fit, which means you'll have to relocate the Engine & Tranny Mounts which ever way you go, so might as well up-date the Tranny @ the same time.
I'd to dp the same thing w/ my '58 Mercury M-100 Truck when I Up-dated to the 300c.i.er & Matching C-4.

 

Thanks. What year Ford pick-up will be the easiest to steel the engine and Tranny out of?

 

Find a '64, '65 or '66 F/M-100 that has a 240/300c.ier & Auto Tranny, as that is the Only years that the engine & tranny mounts are usable as they are in the same place as the 223c.i.er, though you'll still probably have to relocate the Tranny mounts.
Why do you wish to get rid of a perfectly wounderfull engine as the 223c.i.er, there are still performance parts available for them.