American has 75 Airbus A321NX aircraft in the fleet. The A321NX fleet is powered by the CFMI LEAP-1A33 engines. 

American operates the A321NX version of the Neo family featuring Airbus’ Cabin Flex option which eliminates the R2/L2 door. By moving the emergency exit over the wing it adds the capability for more seating capacity. This also means larger overhead bin, mood-lighting and a refreshed cabin layout. American is the launch customer of Airbus' Airspace XL bins, which offer approximately 40 percent more overhead storage space. Power ports and USB ports are at every seat. The A321NX has Viasat satellite Wi-fi which passengers can use their personal device to stream from American's library of movies, T.V. shows, and live television free of charge.

However, in August 2026 American made the decision to reintroduce seatback screens across its narrowbody fleet starting in 2028, featuring 4K displays, Bluetooth audio, Starlink Wi-Fi and USB-C charging. Along with the new interior American plans to add additoinal premium seating on all A321NX and NEO aircraft