We establish a general form of sum-difference inequality in two variables, which includes both more than two distinct nonlinear sums without an assumption of monotonicity and a nonconstant term outside the sums. We employ a technique of monotonization and use a property of stronger monotonicity to give an estimate for the unknown function. Our result enables us to solve those discrete inequalities considered in the work of W.-S. Cheung (2006). Furthermore, we apply our result to a boundary value problem of a partial difference equation for boundedness, uniqueness, and continuous dependence.