The P-51H (NA-126) was the final production Mustang, embodying the experience gained in the development of the XP-51F and XP-51G aircraft. This aircraft, with minor differences as the NA-129, came too late to participate in World War II, but it brought the development of the Mustang to a peak as one of the fastest production piston-engine fighters to see service.

The P-51H used the new V-1650-9 engine, a version of the Packard-built Merlin that included Simmons automatic supercharger boost control with water injection, allowing War Emergency Power as high as 2,218 hp (1,500 kW). Differences between the P-51D included lengthening the fuselage and increasing the height of the tailfin, which greatly reduced the tendency to yaw. The canopy resembled the P-51D style, over a raised pilot's position. Service access to the guns and ammunition was also improved. With the new airframe several hundred pounds lighter, the extra power and a more streamlined radiator, the P-51H was among the fastest propeller fighters ever, able to reach 487 mph (784 km/h or Mach 0.74) at 25,000 ft (7,600 m).

The P-51H was designed to complement the P-47N as the primary aircraft for the invasion of Japan, with 2,000 ordered to be manufactured at Inglewood. Production was just ramping up with 555 delivered when the war ended.

Additional orders, already on the books, were canceled. With the cutback in production, the variants of the P-51H with different versions of the Merlin engine were produced in either limited numbers or terminated. These included the P-51L, similar to the P-51H but utilizing the 2,270 hp (1,690 kW) V-1650-11 engine, which was never built; and its Dallas-built version, the P-51M, or NA-124, which utilized the V-1650-9A engine lacking water injection and therefore rated for lower maximum power, of which one was built out of the original 1629 ordered, serial number 45-11743.

Although some P-51Hs were issued to operational units, none saw combat in World War II, and in postwar service, most were issued to air national guard units. One aircraft was provided to the RAF for testing and evaluation. Serial number 44-64192 was designated BuNo 09064 and used by the U.S. Navy to test transonic airfoil designs and then returned to the Air National Guard in 1952. The P-51H was not used for combat in the Korean War despite its improved handling characteristics, since the P-51D was available in much larger numbers and was a proven commodity.

Many of the aerodynamic advances of the P-51 (including the laminar flow wing) were carried over to North American's next generation of jet-powered fighters, the Navy FJ Fury and Air Force F-86 Sabre. The wings, empennage and canopy of the first straight-winged variant of the Fury (the FJ-1) and the unbuilt preliminary prototypes of the P-86/F-86 strongly resembled those of the Mustang before the aircraft were modified with swept-wing designs.