The ground was first used on 11 October 1904 by Shepherd's Bush F.C., an amateur side that was disbanded during the First World War.QPR moved to Loftus Road in 1917, having had their ground at Park Royal commandeered by the army in 1915. At that time the ground was an open field with a pavilion. One stand from Park Royal was dismantled and re-erected in 1919, forming the Ellerslie Road stand. This stand was the only covered seating in the ground until 1968 and was replaced in 1972. It had a capacity of 2,950. QPR moved out of Loftus Road at the start of the 1931–32 season, moving nearby to White City Stadium, but after a loss of £7,000, the team moved back for the start of the 1933-34 season. In 1938, a new covered terrace for 6,000 spectators was constructed by a company called Framed Structures Ltd at the Loftus Road end taking the overall ground capacity up to 30,000. It cost £7,000 (with £1,500 donated by the QPR Supporters Club) and was opened by the Rt Hon Herbert Morrison, the leading Labour MP and future war time Home Secretary, at the match vs Crystal Palace on 29 October. The section of the terracing that was covered was concreted at this time with the uncovered section later concreted in 1945.
In April 1948, after winning the Third Division (South) championship, the club bought the freehold of the stadium plus 39 houses in Loftus Road and Ellerslie Road for £26,250 financed by a share flotation that raised £30,000. When the club's finances were under pressure in the late 1950s the houses had to be sold. On 5 October 1953 floodlights were used at Loftus Road for the first time for a friendly game against Arsenal. In the summer of 1966 the original floodlights were replaced by much taller floodlight pylons. In the summer of 1980 these in turn were replaced with new floodlights.
QPR experimented once again with a move to White City Stadium in the 1962–63 season, but moved back to Loftus Road once more after less than one full season. In the summer of 1968 the South Africa Road stand was constructed at a cost of £150,000 to replace the old open terracing. In 1972 a new stand was completed in Ellerslie Road, replacing the tin-roofed grandstand erected in 1919, and first used in the match versus Oxford United on 2 December 1972. The changing rooms and offices were moved to South Africa Road and the television gantry moved in the other direction.
The stadium's highest recorded attendance of 35,353 was in a game against Leeds United on 27 April 1974. The following summer the paddock of the South Africa Road stand was converted from terracing to seating with the installation of 4,600 seats, thus lowering the capacity of the stadium to the 31,002 present for the last home match of the 1975/6 season against Leeds United on 24 April 1976.
During the summer of 1981 an artificial pitch of Omniturf was installed at Loftus Road, the first such surface to be used in British professional football. The surface was not favoured by everyone, with QPR keeper Peter Hucker describing it as "basically a bit of carpet over two feet of concrete", and stated that as a goalkeeper, he strongly disliked diving onto it saying that "I'd have close to third degree burns because the pitch would totally rip the skin off." Rangers lost the first league match played on the new surface 1-2 versus Luton Town on 1 September 1981. During the time that Loftus Road had the Omniturf pitch installed, QPR reached two cup finals and became Second Division champions, something that critics claimed was caused by the advantage the pitch presented, and QPR's home games in the 1984–85 UEFA Cup were played at Arsenal'sHighbury Stadium. It was claimed that managerTerry Venables would let opposition teams train on the pitch when it was dry, and then deliberately dampen the pitch so that the ball played differently to what they expected at kick off. It was removed in April 1988 because of football legislation and replaced with grass. There were just three other league stadiums in the whole country with a plastic pitch, and by 1994 all of these had been ripped up.
New stands were opened at the School End in the summer of 1980 and one year later at the Loftus Road end. At the same time as the new Loftus Road stand was built executive boxes were installed in the lower tier of the South Africa Road stand and the artificial pitch laid. The stadium capacity at this time was 27,000 and it was one of the most modern and advanced stadiums in Britain having been completely reconstructed over a 13-year period from 1968 to 1981. In the summer of 1994 the Loftus Road ground became an all-seater stadium with the construction of seating in the lower Loftus Road stand. The last match where home spectators were able to watch the match from terracing was on 16 April 1994 against Everton.
The owning company, also called Loftus Road, of QPR, London Wasps and the stadium itself, went into the red in the late 1990s only a couple of seasons after it was formed in 1996. In 2001, there were concerns that Queens Park Rangers and the stadium would need to be sold separately when the club went into administration. There was interest from commercial buyers and housing developers. A supporter's trust was set up to keep the club at Loftus Road, and to fight the suggested move out of the stadium and to Milton Keynes. One further suggestion was a merger between QPR and fellow London club Wimbledon, with the newly merged club playing at Loftus Road, but this idea was abandoned following the response from supporters. A £1 million payment by QPR's long time local rivals Fulham in 2002 helped to alleviate the financial problems in return for a ground sharing agreement while Craven Cottage was developed. Loftus Road briefly became home to non-league football club Yeading as they faced Premiership club Newcastle United in the third round of the 2005FA Cup. The decision was made as Yeading felt that their home stadium could not suitably segregate the fans. Despite holding out for fifty minutes, Yeading went on to lose the match 2–0. In a fundraiser for the Grenfell Tower fire, which happened on 14 June 2017, Loftus Road stadium hosted a special match - appropriately named 'Game 4 Grenfell' - for the people who lost their lives. Celebrities participating included Olly Murs, Sir Mo Farah and many more. This took place on 2 September 2017.
On 7 June 2019, following nominations and a fan vote from a shortlist, it was announced that Loftus Road Stadium would be renamed the 'Kiyan Prince Foundation Stadium' in honour of the former QPR youth team member Kiyan Prince who was fatally stabbed in 2006.