The first series production model was the Tu-22M-2 Backfire-B (211 built) for the Soviet Air Forces and the Naval Aviation Forces. Normally armed with a single Kh-22 stand-off missile, this variant became operational with 185 Guard Heavy Bomber Aviation Regiment at Poltava in 1978, and also served in Afghanistan.

The ultimate bomber/missile carrying variant is the Tu-22M-3 Backfire-C, (268 built). The M-3 features strengthened wings, raked rectangular intakes serving more powerful engines. It also had a greatly increased weapons load (see specification). The Tu-22M3 remains numerically the most important bomber in the Russian air force's Long-Range Air Army inventory, and serves with seven regiments (one of which also operates Tu-22M-2s). The Naval Aviation Forces have about 80 Tu-22Ms, mostly M-3 models, split equally between divisions subordinated to the Northern and Pacific Fleets. The Naval Aviation Forces also have 12 M-3s converted as Tu-22MR reconnaissance aircraft, and reportedly also operates limited numbers of recce-configured Tu-22M2Rs.

Because of delays in the development of the Sukhoi T-60, the intended replacement of the Tu-22M3, it has been decided to embark on a major upgrade of the Backfire. The Tu-22M-2/M-3s of both the Air Force and Naval Aviation will be upgraded to Tu-245 standard, with a new radar, new missile systems and an automatic terrain-following capability. Russia is also trialling small numbers of redundant Tu-22M-3 airframes converted as Tu-22MP prototypes of a planned electronic warfare/escort jammer variant. The sole non-Russian operator of the potent Backfire is Ukraine, which gained former Black Sea Fleet Naval Aviation Regiments of Tu-22M-2/M-3s. About 50 bombers equip three air force heavy bomber regiments.