The club remained a tiny amateur outfit until 1949, when it turned professional, coinciding with a major overhaul of the facilities at the Manor Ground.
It was also at this moment in history that United pulled away from their counterparts Oxford City, who remained amateur. This allowed for a shift in the balance of power in the city that has remained up until the present day.
Headington made attempts to join the Football League, but were turned down in 1950, losing out to Colchester and Gillingham. Four years later the team made the national headlines with a run to the fourth round of the FA Cup.
In an attempt to persuade the Football League that the city could not be ignored again and to encourage more fans from all over Oxford to identify with the club, Headington United became Oxford United in 1960 and it wasn't long before success arrived.
Under the leadership of Arthur Turner, Oxford won two Southern League titles and were elected into the League in 1962, following the demise of Accrington Stanley.
In 1964, Oxford had the distinction of becoming the first Fourth Division side to reach the sixth round of the FA Cup, knocking out League leaders Blackburn in the process. They were eventually beaten by Preston in front of 22,750 at the Manor.
One year on, they earned promotion from Division Four and in 1968, won the Division Three Title, with Ron Atkinson as skipper, as Turner's golden touch continued.
After eight years in Division Two, Oxford were relegated for the first time in their League history and a financial crisis followed, before Robert Maxwell stepped in to save the club from bankruptcy in 1982.
Maxwell put forward a controversial proposal to merge Oxford with Reading, forming the Thames Valley Royals, but this idea was soon discarded and under Jim Smith the good times returned to the Manor.
The Division Three Title was won in 1984, followed by the Division Two championship a year later and Oxford were in the top flight for the first time. Oxford became the first club ever to win successive titles, but Smith made a shock exit to take up the manager's post at QPR.
Maurice Evans took over as boss and his side beat Smith's QPR 3-0 in the 1986 League Cup final at Wembley in front of over 90,000 fans. They were denied entry into Europe as a consequence of the Heysel ban.
Oxford had avoided relegation from Division One by winning on the final day of the 1986 season and the following two years were also battles against the drop. Despite the goals of deadly young striker Dean Saunders, United were demoted after three years at the top, after Maxwell had turned his attentions to Derby County.
Mark Lawrenson was installed as manager in 1988, but only lasted for seven months, leaving Brian Horton as the man responsible for halting the club's slide. Money was tight and players had to be sold to keep the club afloat. After avoiding relegation on the last day of the season again, the club eventually returned to Division Two (formerly Division Three) in 1994.
Under Denis Smith, they returned to Division One in 1996 and were given planning permission to move to a 15,000-seater stadium at Minchery Farm, south of the city. Robin Herd took over as chairman and Oxford were flying as high as fifth in Division One in December. After selling defender Matt Elliott to Leicester for a club record £1.6 million, the U's ended up in the lower reaches of midtable.
Chairman Herd resigned during the 1997/98 season and the club was once again dogged by financial problems. Malcolm Crosby took temporary charge of playing affairs, before League Cup winning captain Malcolm Shotton was chosen as new manager after Cheltenham's Steve Cotterill had originally been linked with the job.
Shotton made a big impact, guiding the U's to a 12th place finish and Dean Windass was brought in for a record £475,000 as optimism circled around the Manor. However, an anticipated take-over hit difficulties and players once again had to be sold. Windass was snapped up by Bradford City and despite a great show against Chelsea in the FA Cup, United were relegated to Division Two in 1999.
London hotelier, Firoz Kassam, took over as Chairman, but a poor start to the season saw Shotton's resignation. Denis Smith returned for a second spell and put his faith in youth, managing to prevent a second successive relegation with a game to spare.
Joe Kinnear was brought in as Director of Football in October 2000, with David Kemp as first team boss and Smith moving into a scouting role. Kinnear and Kemp departed early in 2001 and Oxford's final year at the Manor Ground ended in relegation to the Third Division.
Former England defender Mark Wright was given the job in May 2001, after a spell at Conference side Southport and the club were finally able to relocate to the Kassam Stadium.
Wright's spell at the club where he started out as a youngster was short-lived and, with Ian Atkins taking over at the helm, a disappointing campaign saw Oxford end up in 21st place.
Atkins released 17 players in the summer of 2002 and rebuilt the squad that he inherited. It was a big step in the right direction as Atkins' side set a record for away wins in one season and enjoyed a sweet televised FA Cup victory over Swindon.
A trip to Highbury in the FA Cup ended in a 2-0 defeat and the U's missed out on a play-off place by a single point.
Last year saw the U's again knocking on the play-off door, but they finished 9th and will hoping for an improvement this time around under the leadership of Argenitine Ramon Diaz.