Northampton Saints was established in 1880 under the original title of Northampton St. James by Rev Samuel Wathen Wigg, a local clergyman and curate of St. James. This is how the club got its two nicknames of The Saints or Jimmies. Wigg’s original concept was to promote "order" to his younger parish members by creating a youth rugby club, with the philosophy of a "hooligan sport designed to turn them into gentlemen".

It was not long before The Saints had become one of the major rugby union teams in the country. Twenty years after its establishment, the first Saints player, local farmer Harry Weston, was awarded an England cap.

In the early years of the 20th century, a player named Edgar Mobbs, who was a hero throughout the town, dominated the club. Edgar. He was the first Northampton player to captain his country but he is best remembered for his exploits in World War I. After initially being turned down as too old, Edgar raised his own "Sportsman's" battalion otherwise known as Mobbs Own. Sadly, Edgar was killed in battle after leading his battalion over the top, by kicking a rugby ball into No-Mans land on 29 July 1917 and attacking a machine gun post, his body was never found. The club arranged the Mobbs Memorial Match as a tribute. It has been played every year since 1921 between the Barbarians and East Midlands at Franklin's Gardens.

After the war the Saints continued to grow and they started to produce some of the best players in England, some of whom went on to captain their country. Over the years they have been producing players such as Butterfield, Jeeps, Longland, White and Jacobs.

During the 80’s the Saints failed to keep pace with movements within the game and top players were no longer attracted to the Gardens, where a 'them and us' mentality had built up between the players and the management. Some former players formed their own task force which ousted the old brigade in the 1988 'Saints Revolution' and put a plan into action which would put the club back at the top of the English game.

Barry Corless, as director of rugby, set about restructuring the club and soon the Saints were back on the way up, helped by the signing of All Blacks legend Wayne 'Buck' Shelford.

In 1990, Northampton Rugby Union Football Club gained promotion to the then First Division and the following year made their first trip to Twickenham to play Quins in the Pilkington Cup Final. They lost in extra time but the foundations of a good Saints line-up were beginning to show in the following few seasons.

In 1994, Ian McGeechan took over as Director of Rugby, and although the club were relegated in his first season, they returned in style the next season, winning every single game of their campaign and averaging 50 points a game. This season is referred to by many fans of the club as the "Demolition Tour of Division Two".

In 1999, Saints came runners-up in the Allied Dunbar Premiership, their league campaign climaxing with a crucial home local derby with eventual winners Leicester Tigers which they lost 15-22. Ian McGeechan had left the club at the end of the previous season to return to coach Scotland, and was replaced by former Saints player John Steele who had done well on a limited budget at London Scottish. Steele relied on the foundations laid by McGeechan, as well as the inspirational captaincy of Samoan Pat Lam to lead the club to European success the following season.

In 1999-2000, the club became a Public Limited Company (Plc) and shares were issued to the public. During this season the Saints lost in the Tetley's Bitter Cup Final to Wasps, but beat Munster 9-8 in the European Cup Final to win their first major trophy.
After a poor start to the 2001/2002 season, former All-Black coach Wayne Smith was appointed as Head Coach. He went on to transform the club in five short months. A team who looked down and out in November were moulded into a side that reached the Powergen Cup final and again qualified for the Heineken Cup. The Saints made successive cup final appearances in 2002 and 2003 and reaching the Premiership play-off semi-finals in 2003 and 2004.

Relegation was narrowly avoided in 2005 after the then coach, Alan Solomons was sacked in the middle of the season. The coaching role went to the former first team mates Budge Pountney and Paul Grayson to tide the team over.

They had a slow start in the 2005-6 season, but continued to stay mainly unbeaten after the New Year. Budge retired at the start of the 2006-7 season leaving Grayson in overall control.

The Saints competed in the 2006-07 Heineken Cup where they finished second in their pool, behind Biarritz Olympique. Northampton qualified for the quarter-finals and actually met Biarritz in Spain. Despite being in last place of the English league at the time, they defeated the French champions 7-6 to advance to the semi-finals.

In April 2007, despite a 27-22 victory over London Irish at Franklin's Gardens, Northampton were relegated from the Guinness Premiership. A "behind the scenes restructure" led to the brief appointment of Peter Sloane as Head Coach, from the role of forwards coach. Paul Grayson was demoted to skills and backs coach.

In March 2008, Northampton beat Exeter Chiefs to ensure their promotion and a return to the Guinness Premiership. In April 2008, they beat Exeter Chiefs at Twickenham Stadium to win the EDF trophy. They ended their National Division One season undefeated with 30 wins from 30 games.
In the 2008–09 season, the Saints easily avoided the drop, finishing eighth on the table. They also lifted the European Challenge Cup, defeating French side Bourgoin 15–3 in the final on 22 May 2009 at The Stoop in London. The victory gave them a place in the 2009–10 Heineken Cup.

The team finished the 2009/10 season in second place in the Guinness Premiership, achieving a home semi-final against Saracens F.C., which was lost 19-21. In the same season, Northampton defeated Gloucester Rugby 30-24 to win the LV= Cup and progressed as far as the quarter-finals of the Heineken Cup, being the only English team to reach that stage.