AA's main focus is on domestic routes in the US, but the airline operates direct flights to all continents except Africa.

In cooperation with its Oneworld alliance partners (mainly British Airways and Iberia), it often offers the cheapest fares from Europe to the US, mainly from Germany, the UK or Austria.

American Airlines operates a direct service between Prague and Philadelphia and, from 8 May 2020, Chicago.

Conversely, standalone domestic flights within the US tend to be very expensive with prices starting at 220 eur for a return ticket. The ideal time to book flights with AA is classically 2-4 months before departure.