The 1999 Ford F-Series Super Duty F250 was available as a rear or four wheel-drive pickup and provided an increased hauling capacity over the Ford F-Series F150 models. The 1999 F250 could pull up to 11,000 pounds and carry more weight. It was available in three different cab styles: RegularCab, SuperCab, and CrewCab; as well as thirty different trims, including XL, XLT SuperCab SWB, Lariat CrewCab LWB, and XL CrewCab LWB.

Standard in all four-wheel and rear-wheel drive 1999 Ford Super Duty F250 pickups was a 5.4 L 235 hp V8 engine producing 335 ft lbs of torque @ 3000 rpm. Other options included a 7.3 L 235 hp 16-valve gas engine producing 500 ft lbs of torque @ 3000 rpm and 6.8 L 275 hp 20-valve gas engine producing 410 ft lbs of torque @ 2650 rpm.

Standard in all rear-wheel and four-wheel drive 1999 Ford Super Duty F250 pickups was a 5-speed manual overdrive transmission. A 4-speed automatic overdrive transmission or 6-speed manual overdrive transmission were available as options.

The 1999 F250 was available in a basic black, light prairie, bright amber, and dark hunter green. Dark toreador, oxford white, red, and woodland green were also available as options.

Standard equipment in all 1999 Ford Super Duty F250 pickups was a radio, ABS brakes, airbags for the driver and passenger, tachometer, and child safety door locks. Cargo area cover and pickup bed liner were available for all trims, along with Cruise Control, tilt steering, keyless entry, and leather steering wheel.

Air conditioning was standard in XL, XLT, XL SuperCab, XL CrewCab, XLT CrewCab, and Lariat CrewCab trims. Power windows, power door locks, and leather seats were standard equipment in Lariat models. Power seats were available for all XLT trims. A cassette player was standard equipment in all XLT and Lariat 1999 F250 pickups, while a CD player was an option available for all 1999 Ford Super Duty pickups.