American made the first scheduled non-stop transcontinental flights in 1953 with the 80-passenger DC-7. It was introduced on its New York-Los Angeles route and was the first airliner to provide nonstop transcontinental service in both directions. It was the fastest transport aircraft in service, at the time.

But Like other piston-engine airliners the Dc-7, was made obsolete by the introduction of turbine-engine like the Boeing 707 or DC-8. In 1955 American ordered its first jetliners, Boeing 707s, which were delivered in 1959. For the short and medium haul it ordered the Boeing 727, delivered in 1965. With larger and faster aircraft on the drawing boards, American became interested in, and eventually purchased also jumbo B-747s in the late 1960s. 

On October 1, 1982, the creation of a holding company, the AMR Corporation was founded, which included American Airlines. This move would not affect daily business, but would “provide the company with access to sources of financing that otherwise might be unavailable. 

American updated its jetliner fleet to meet the new conditions in the industry during the 1980s by introducing the B-767s in 1982 and MD-80s in 1983. The newer aircraft had two major advantages over other wide-bodied aircraft: a two-person cockpit crew and higher fuel efficiency. The Boeing 767 went on to become the workhorse of the American long-haul fleet, flying transcontinental and transatlantic routes for decades.

In the late 1980s, American Airlines opened three hubs for north-south traffic. San Jose International Airport was added after American purchased AirCal. American built a terminal and runway at Raleigh-Durham International Airport and Nashville International Airport was also added as a hub. In 1987 it received the first jets from Airbus, the A300 which was in use till 2010. The end of the 1980's also saw the Boeing B737-100 come into serive in 1987 and the Boeing B757 in 1989. 

In 1990, American Airlines bought the assets of TWA's operations at London Heathrow. As well lower fuel prices and a favourable business climate led to higher profits in the 1990s which saw American grow a lot it's business and presence. 

Miami International Airport became a hub after American Airlines bought Central and South American routes ("El Interamericano") from Eastern Air Lines in 1990 (inherited from Braniff International Airways but originated by Pan American-Grace Airways which was known as Panagra). Through the 1990s, American Airlines expanded its network in Latin America to become the dominant U.S. carrier in the region. In 1991 the airline received the MD-11 which it operated to trunk routes to south America, Europe and trans-pacific. 

On October 15, 1998, American Airlines became the first airline to offer electronic ticketing in the 44 countries it served. In 1999, American Airlines, British Airways, Cathay Pacific, Canadian Airlines, and Qantas founded the global airline alliance Oneworld. 

In the 1990's three new hubs were abandoned, some San Jose facilities were sold to Reno Air and Raleigh/Durham sold to Midway Airlines. (Midway went out of business in 2003). American Airlines purchased Reno Air in February 1999 and integrated its operations on 31 August 1999 but did not resume hub operations in San Jose. American discontinued most of Reno Air's routes, and sold most of the Reno Air aircraft, as it did with Air California 12 years earlier. At this time American also received it's first Boeing 737-800 next generation as well the first of the Boeing B777-200 in 1999. 

In 1998 American was looking for further merges, that led to Trans World Airlines who was already close to final bankruptcy to be taken over by American Airlines. (it would file for its third bankruptcy as part of the purchase agreement and the take over of its hub in St. Louis). In April 2001, American Airlines completed acquisition of TWA's assets. At about the same time, American Eagle accepted delivery of 15 44-seat regional jets (ERJ-140) manufactured by Embraer of Brazil. American also announced plans to accelerate retirement of 36 aircraft: 19 DC-9s, 12 Boeing 727s, 4 MD-11s and the Fokker 100.

Then the unimaginable happened... when two planes of American Airlines were used on the unexpected events in the morning of September 11, 2001. American Airlines began losing money in the economic downturn that followed the September 11, attacks. Severe measures were put in place, wage and benefit agreement cuts with the unions, the St. Louis hub was downsized, early retirement of planes, terminated unprofitable routes, reduced seat pitch, ended three-class service on many international flights, and standardised its fleet. 

To make things worse, American had repeated run-ins with the FAA regarding maintenance of its MD-80 fleet, cancelling 1,000 flights to inspect wire bundles. This made American to begin the process of replacing its older MD-80 jets with Boeing 737s and later on with Airbus A319s and A321s.

However, from 2003 to 2005, the airline also expanded into new markets, including Ireland, India, and mainland China. On July 20, 2005, American announced a quarterly profit for the first time in 17 quarters. 

The 2008 financial crisis again placed strain on the airline. On July 2, 2008, American reduced its workforce by 950 flight attendants, as well as the retirement of 20 MD-80 aircraft. Also all Airbus A300 jets were retired by the end of August 2009. American also closed its Kansas City overhaul base, inherited from TWA on September 24, 2010.

American was a key player in the 2009–11 restructuring of Japan Airlines. In September 2009, AMR Corporation invested in the financially struggling JAL. This led to an enhanced joint venture between American and JAL beginning April 1, 2011. American also began an interlining partnership with JetBlue Airways in March 2010 which covered 27 JetBlue destinations not served by American and 13 American international destinations from New York and Boston. 

American expanded its service to Asia and the Pacific. It was one of the initial US bidders in February 2010 to serve Tokyo's Haneda Airport, and was awarded rights to serve Haneda from New York JFK, however it later cancelled its JFK-Haneda service in October 2013 due to the service being "quite unprofitable". 

In order to make a successful turnaround, American placed the "largest aircraft order in history" in July 2011, purchasing 460 "next generation" Boeing 737 and Airbus A320 aircraft for delivery between 2013 and 2022. These aircraft were designated to replace American's short and medium-haul fleet of 757-200, 767-200, and MD-80 aircraft, eventually consolidating the fleet around four aircraft families (Boeing 737, Airbus A320, Boeing 787, and Boeing 777). 

However its expansion came at a cost to AMR Corporation, then the parent company of American, big losses left no choice but to file for Chapter 11 bankruptcy protection on November 29, 2011, and American began capacity cuts on July 1, 2012 due to the grounding of several aircraft associated with its bankruptcy and lack of pilots due to retirements. American's regional airline, American Eagle, was to retire 35 to 40 regional jets as well as its Saab turboprop fleet. American ceased its service to Delhi, India in March 2012 as well as other unprofitable routes. 

In January 2012, US Airways Group, the parent company of US Airways, expressed interest in taking over AMR Corporation, the parent company of American Airlines. With AMR under Chapter 11 bankruptcy protection, American Airlines had been looking to merge with another airline. Earlier in July, a bankruptcy court filing stated that US Airways was an American Airlines creditor and "prospective merger partner". 

Meanwhile American also began service between Los Angeles and Shanghai in 2011 and between Dallas/Fort Worth and Seoul in 2013 and from Dallas/Fort Worth International Airport to both Shanghai and Hong Kong in the summer of 2014, providing the first ever nonstop service between Dallas/Fort Worth and China. 

On January 17, 2013, American introduced a new logo, livery, and brand image, unveiling the livery on its first Boeing 777-300ER aircraft which went into service later that month. 

On February 14, 2013, AMR Corporation and US Airways Group officially announced that the two companies would merge to form the largest airline (and airline holding company) creating the new holding company American Airlines Group, Inc. On April 8, 2015, after a long battle in the courts, the Federal Aviation Administration awarded American Airlines and US Airways a single operating certificate. The US Airways brand was discontinued on October 17, 2015 and all flights branded as "American Airlines". 

American launched daily service from Los Angeles to Tokyo-Haneda on February 11, 2016 using their Boeing 787 aircraft. American also added daily service from Los Angeles to Sydney, Auckland and Hong Kong on their flagship Boeing 777-300ER and Boeing 787-8 (to Auckland), returning to Australia and New Zealand for the first time since the 1990s.