In 1970, the airline began what turned out to be very lengthy negotiations aimed at obtaining approval to operate services to the US.

They key development for the airline to be known as we know it today, happened just two years later in 1972. The differing needs of the two shareholders, led to the break-up of Malaysia-Singapore Airlines (MSA) just 6 years later. The Singapore government preferred to develop the airline's international routes, while the Malaysian government had no choice but to develop the domestic network first before going regional and eventually international. MSA ceased operations in 1972, with its assets split between two new airlines; Malaysian Airline System (MAS), and Singapore Airlines (SIA). With the Singapore government determined to develop its airlines' international routes, it took the entire fleet of seven Boeing 707s and five Boeing 737s, which would allow it to continue servicing its regional and long-haul international routes. Since most of MSA's international routes were flown out of Singapore, the majority of international routes were in the hands of Singapore Airlines.

Its new name, Singapore Airlines, and the callsign "SIA" with a blue-yellow livery was officially launched on 1 October 1972. SIA expanded almost overnight after the split from MSA in 1972, adding cities in the Indian subcontinent and Asia to its network, and new airliners, including Boeing 747s, to its fleet. The first two 747-200s arrived in the summer of 1973 and were deployed on the lucrative Singapore-Hong Kong-Taipei-Tokyo (Haneda Airport) run.

As of 1976, SIA had an all-Boeing fleet of 21 aircraft: 5 Boeing 737-100s, 11 Boeing 707-300s, and 5 Boeing 747-200s. The airline's passenger network covered 28 cities in 23 countries, ranging from London in the north west to Auckland in the south east. The 737s flew regional services, including most of the company's 52 flights per week to Kuala Lumpur. The larger airliners operated on longer distance routes. Flights to London were operated daily by 747s and 707 flights departed for Amsterdam.

That year, SIA also operated daily 747 flights to Tokyo, daily 707 flights to Osaka, and daily flights to Sydney using a mix of 747s and 707s. Other flights went more frequently to Jakarta, Bangkok and Hong Kong, and less frequently to Perth, Melbourne and Auckland.

In August 1976, negotiations between SIA and the US Civil Aeronautics Board (CAB) over possible SIA services to the US stalled over the key issue of the routes that SIA could take. SIA wanted to operate via Tokyo, the most lucrative transit point at the time, but the CAB thought that such a routing would have too significant an effect on the profits of SIA's US-based competitor, Pan Am. The CAB reportedly insisted that SIA would have to fly "in parallel" with Pan Am services to Singapore to earn approval, on a Singapore – Guam – Honolulu – San Francisco routing.

In March 1977, negotiations between SIA and the CAB were resumed, and in August 1977 it was reported that the airline had placed an order for four McDonnell Douglas DC-10s. The same month, SIA took delivery of its first Boeing 727-200 Advanced, flying the aircraft on its inaugural service from Singapore to Manila. The B727 was SIA's successor to the B737-100s that it had inherited from MSA.

In late September 1977, at the end of seven rounds of negotiations, SIA and the CAB finally agreed that the airline could operate passenger services to the US, on a route to San Francisco via Hong Kong, Guam and Honolulu, initially three times per week, and increasing to five times per week by 1980.

In December 1977, British Airways and SIA shared a Concorde for flights between London and Singapore via Bahrain. The aircraft, BA's Concorde, was painted in Singapore Airlines livery on the port side and British Airways livery on the starboard side. The service was discontinued after only 4 days and three return flights because of noise complaints from the Malaysian government. British Airways and Singapore Airlines resumed flights on 24 January 1979, this time avoiding Malaysian airspace as well as Indian's. However, the service was discontinued for good on 1 November 1980.

In 1978, Singapore Airlines (SIA) strategically expanded its long-haul capabilities by introducing the McDonnell Douglas DC-10-30 to its fleet. The airline received its first aircraft (registration 9V-SDA) on November 15, 1978. The DC-10 was the pioneer on the inaugurating service to the United States on April 4, 1979. This landmark flight connected Singapore to San Francisco via Hong Kong and Honolulu, featuring the iconic "California here we come"

Meanwhile, SIA extensively publicised its new passenger services to the US. Then, on 25 May 1979, an American Airlines DC-10 crashed in Chicago, causing 273 fatalities. Soon afterwards, and as a consequence of the crash, the US Federal Aviation Administration banned the flying of DC-10s in US airspace. SIA therefore had to switch its new US services to operation by 707s until late August 1979, when its new Boeing 747-200 'Super Bs' took over the route. The airline also sold all of its DC-10s by late 1983.

On 12 May 1981, Singapore Airlines' first direct flight from London Heathrow Airport to the new Singapore Changi Airport (including Terminal 1) took place. During the years that followed, SIA expanded services to United States, Canada, and additional European cities, with Madrid becoming the first Hispanic city to be served by the airline. Boeing 747-300s were leased and introduced into the SIA fleet in 1983 and named 'Big Tops'.

Again a short-term affair was begun with a few Boeing 757s later followed by the addition of Airbus A310s and Airbus A300s The A310s became the Asian regional workhorse of the fleet, with the small A310-200 fleet serving until the late 1990s, and the much larger A310-300 fleet serving into the 2000s having 17 units of the type at its height.

In 1989, the first of 43 B747-400s was added to the fleet, famously dubbed the "Megatop,", it was used first on the Singapore to London route. A few years later, the Airbus A340-300s augmented the 747-400s on long-range routes to Spain, Zürich, Copenhagen, San Francisco and cities not suitable for 747 service. Services extended to southern Africa in the 1990s when the airline began flights to Johannesburg in South Africa; Cape Town and Durban were later added. The 1990s also saw the opening of Terminal 2 in Changi Airport in 1991; all flight operations later moved to the new terminal.

Towards the end of the 1990's Singapore Airlines (SIA) ushered in a new era of regional and long-haul travel with the strategic introduction of the Boeing 777 family. The airline took delivery of its first Boeing 777-200 on May 6, 1997, which officially entered commercial service on May 14, 1997, with an inaugural flight from Singapore to Jakarta. Shortly after, on December 10, 1998, SIA introduced the stretched Boeing 777-300 to its fleet, deploying it primarily on high-capacity regional routes such as Sydney, Tokyo-Narita, and Hong Kong.

Singapore Airlines officially became a member of Star Alliance on April 1, 2000. By joining the world’s first and largest global airline alliance, SIA significantly expanded its reach, offering passengers seamless connections to hundreds of destinations across the globe.

In April 2004, SIA began non-stop trans-Pacific flights from Singapore to Los Angeles and Newark, utilising the Airbus A340-500. These flights marked the first non-stop air services between Singapore and the US. The Singapore to Newark flight held the record for the longest scheduled commercial flight, with a flying time of about 18 hours each way. Singapore Airlines converted its five Airbus A340-500 aircraft to a 100-seat all-Business Class configuration for its routes to Newark and Los Angeles.

On 25 October 2007, SIA's first double decker Airbus A380-800 operated the type's inaugural revenue service, a flight from Singapore to Sydney. SIA choose to operate the A380 on routes to London, Zürich, Frankfurt, Paris, Mumbai, Beijing, Sydney, Melbourne, Los Angeles and New York.

In January 2009, SIA decided to stop its thrice weekly flights to Vancouver, Canada, due to less demand after the 2008 financial crisis. The last flight took place on 25 April 2009.

On 6 April 2012, Singapore Airlines phased out the last passenger 747-400 in its fleet after 39 years of service. A final round-trip commemorative flight was operated from Singapore to Hong Kong and back with flight numbers SQ747 and SQ748 respectively. As well as an extended flying time, special meals, performances and inflight celebrations, passengers were given well stocked 747 goody bags.

After much careful consideration, the airline announced that it will end its direct flights from Singapore to both Newark and Los Angeles from 23 November 2013 and 20 October 2013, respectively. However, Los Angeles was continued to be served from Singapore via Tokyo-Narita.

In 2013, the airline initiated a massive $17 billion fleet renewal program, which included an initial order for 30 Airbus A350-900 aircraft and 30 Boeing 787-10 Dreamliners, the latter of which saw SIA serve as the global launch customer. The agreement with Airbus was to be the launch customer of the new version of the Airbus A350 XWB called the A350-900ULR (for "Ultra Long Range"). This year also marked a significant upgrade to its existing long-haul product, as the airline unveiled a new generation of cabin interior products on select Boeing 777-300ER aircraft. 

The 2014–2015 period saw the formalization of plans to introduce a Premium Economy Class, a significant shift in the airline's long-standing three-class model. This $80 million investment was officially launched on August 9, 2015, on a flight from Singapore to Sydney. The new class was gradually rolled out across the Airbus A380 and Boeing 777-300ER fleets.

The year 2016 stood as one of the most operationally significant years in the airline’s recent history, headlined by the delivery of its first Airbus A350-900 on the 2nd March 2016. This aircraft became the backbone of SIA's medium-to-long-haul strategy, allowing the carrier to launch new non-stop services to cities like Amsterdam, Johannesburg, and Düsseldorf. On October 14, 2016, SIA reached a historic milestone by taking delivery of its sixth A350-900, which also happened to be the 10,000th aircraft ever delivered by Airbus. Furthermore, September 2016 saw the debut of the "Capital Express" route, which uniquely linked Singapore with Canberra, Australia, and Wellington, New Zealand, making SIA the first airline to operate regularly scheduled international services to the Australian capital.