ALLEN PARK, Mich.—In this suburb just west of Detroit, Ford Motor Co. F -0.11%is working on one of the biggest gambles in its 108-year history: a pickup truck with a largely aluminum body.

The radical redesign will help meet tougher federal fuel-economy targets now starting to have wide-ranging effects on Detroit's auto makers. But Ford will have to overcome a host of manufacturing obstacles, plus convince die-hard pickup buyers that aluminum is as tough as steel.

Ford...