A mainline flight is one that is operated by an airline's main operating unit, rather than by regional alliances, regional code-shares or regional subsidiaries. Examples of mainline passenger airline flights include those operated by American Airlines, Delta Air Lines, and United Airlines but it would not include flights operated by regional airlines American Eagle Airlines or Comair with Regional jets or the services of mainline regional brands such as American Connection, Delta Connection, or United Express aboard lower-capacity narrowbody jets and turboprop aircraft, such as those produced by Embraer or Bombardier, that do not have transcontinental range. Often US mainline airline carriers operate in-house brands such as the Delta Shuttle, or the mainline United's Ted, and United p.s. to cater to different business segments such as the short-range air shuttle, low-cost, or premium-service flights which normally would not support the traffic or revenue yield needed for the traditional operation of larger mainline aircraft with over 100 passenger seats between selected city pairs.

All of the mainline airlines listed below operate international, intercontinental, or transoceanic airline services using jet airliners

All of the following airlines and their holding companies operate using secondary regional carriers via airline marketing sub-brands commonly marketed as "Express" or "Connection" services.

All of the following airlines in some shape or form, operate in association with a regional component. All legacy carriers also happen to be among the group of US airlines known as "mainline" carriers.