Direct proof of use
The AGM-86C/D Conventional Air-Launched Cruise Missile was used by U.S.-led forces in the 2001 War in Afghanistan. The U.S. Air Force AGM-86B/C/D fact sheet lists the CALCM as having been employed effectively in combat in Operation Enduring Freedom, the U.S. campaign name for the opening Afghanistan war period.
Public sources do not give a reliable open launch count or target-by-target list for AGM-86 employment in Afghanistan. The direct public claim is therefore narrower than the missile's better-documented use in the 1990 Gulf War and 2003 Iraq War: CALCMs were part of U.S. Air Force combat employment in Operation Enduring Freedom, launched from the B-52 force.
Sources: AGM-86B/C/D Missiles | U.S. Air Force, Senate Operation Enduring Freedom Hearing
Timeline
Operation Enduring Freedom began on October 7, 2001, with strikes against Taliban and al-Qaeda targets around Herat, Shindand, Shibarghan, Mazar-i-Sharif, and Kandahar. RAND's air-campaign history records 10 B-52 heavy bombers operating from Diego Garcia among the opening-night strike aircraft.
A February 2002 Senate Armed Services Committee hearing placed the B-52 in Operation Enduring Freedom as a platform U.S. commanders had counted on, noting its mixed weapons loads and its carriage of the Conventional Air-Launched Cruise Missile. The Air Force's AGM-86 fact sheet later summarized the missile family's combat record by listing Operation Enduring Freedom among CALCM combat employments.
Sources: RAND Air Power Against Terror, Senate Operation Enduring Freedom Hearing, AGM-86B/C/D Missiles | U.S. Air Force
Operational role
In Afghanistan, the CALCM's documented role was long-range conventional standoff strike by U.S. B-52 bombers rather than transfer to Afghan forces or use by another coalition aircraft. The Air Force fact sheet identifies the AGM-86C as a conventional blast-fragmentation CALCM and the AGM-86D as a conventional penetrating-warhead variant, both using GPS-aided inertial navigation.
Senate testimony described the Conventional Air-Launched Cruise Missile as a B-52 weapon able to reach targets hundreds of miles from the launch area, keeping the bomber outside hostile air defenses. RAND's history of the Afghanistan air campaign separately describes the opening air operation's preplanned targets, including airfields, command-and-control facilities, ground forces, early warning radars, and al-Qaeda infrastructure.
Sources: AGM-86B/C/D Missiles | U.S. Air Force, Senate Operation Enduring Freedom Hearing, RAND Air Power Against Terror