Either way, you've got to know. One historical way way is:
IS_64BIT = sys.maxint > 2 ** 32
Except that sys.maxint is specific to Python 2. Being the crossover point where ints transparently become longs, sys.maxint doesn't apply in Python 3, where ints and longs have been merged into just one type: int (even though the C calls it PyLongObject). And Python 3's introduction of sys.maxsize doesn't help much if you're trying to support Python <2.7, where it doesn't exist.
So instead we can use the struct module:
IS_64BIT = struct.calcsize("P") > 4
This is a little less clear, but being backwards and forwards compatible, and given struct is still part of the standard library, it's a pretty good approach, and is the one taken in boltons.ecoutils.
But let's say you really wanted to get it down to a single line, and even standard library imports were out of the question, for some reason. You could do something like this:
IS_64BIT = tuple.__itemsize__ > 4
While not extensively documented, a lot of built-in types have __itemsize__ and __basicsize__ attributes, which describes the memory requirement of the underlying structure. For tuples, each item requires a pointer. Pointer size * 8 = bits in the architecture. 4 * 8 = 32-bit architecture, and 8 * 8 = 64-bit architecture.
Even though documentation isn't great, the __itemsize__ approach works back to at least Python 2.6 and forward to Python 3.7. Memory profilers like pympler use __itemsize__ and it might work for you, too!