Sheringham played as a forward, mostly as a second striker, in a 24-year professional career. Sheringham began his career at Millwall, where he scored 111 goals between 1983 and 1991, and is the club's second all-time leading scorer. He left to join First Division Nottingham Forest. A year later, Sheringham scored Forest's first ever Premiership goal, and was signed by Tottenham Hotspur. After five seasons at Spurs, Sheringham joined Manchester United where he won three Premiership titles, one FA Cup, one UEFA Champions League, an Intercontinental Cup and an FA Charity Shield. In 2001, he was named both the PFA Players' Player of the Year and FWA Footballer of the Year. The
After leaving Manchester United at the end of the 2000–01 season, Sheringham re-joined Tottenham Hotspur, where he was a losing finalist in the 2001–02 Football League Cup. He spent one season at newly promoted Portsmouth, scoring the club's first Premier League goal, before joining West Ham United, where he helped the club gain promotion from the 2004–05 Football League Championship. The following season, Sheringham appeared for West Ham in the 2006 FA Cup Final, becoming the third-oldest player to appear in an FA Cup Final.
Sheringham is currently the eleventh-highest goalscorer in the history of the Premiership with 146 goals, and is the competition's 19th-highest appearance maker. He holds the record as the oldest outfield player to appear in a Premier League match (40 years, 272 days) and the oldest player to score in a Premier League match (40 years, 268 days).
Sheringham retired from competitive football at the end of the 2007–08 season with Colchester United, at the age of 42. He has since managed League Two club Stevenage, and ATK of the Indian Super League.
In June 1997, Sheringham agreed to join Manchester United in a £3.5 million deal. He was signed to replace the iconic Eric Cantona whose retirement had left the Old Trafford faithful demanding a big name to fill the gap. His first competitive game for the club was against Chelsea in the 1997 FA Charity Shield which United won on penalties. His first league outing was against his former employers, Tottenham, at White Hart Lane. Throughout the game, Sheringham suffered jeers and boos from his former fans, who had been angered by the fact that Sheringham had accused Tottenham of lacking ambition when he made his transfer. In the 60th minute with the score at 0–0, Sheringham missed a penalty, although ended up on the winning side as two late goals gave United the win.
Sheringham's first season at Old Trafford was difficult – although he scored 14 goals in all competitions he failed to meet expectations as the 1997–98 season ended without the league title. Towards the end of the season, during a game at Bolton Wanderers, an incident occurred that furthered the animosity with fellow striker Andy Cole. When Bolton scored, Sheringham blamed Cole, his strike partner and Cole then refused to talk to him. The breakdown in their relationship was never resolved, and reputedly they never spoke again. This had started three years previously in 1995 when Sheringham had snubbed Cole as the latter came on to make his international debut.
Speculation that Sheringham would leave United increased just after the 1998–99 season got underway, when Dwight Yorke moved to Old Trafford from Aston Villa. Yorke immediately formed a prolific partnership with Cole as United went on to regain the league title on the final day of the season. Sheringham's first-team chances were relatively limited but he still managed to make enough appearances to qualify for a championship medal at the end of the season – at the age of 33 he had won his first major trophy. A week later he came off the substitutes bench to score United's opening goal in a 2–0 defeat of Newcastle United in the FA Cup final to secure the double. Four days after the FA Cup triumph, Sheringham scored a dramatic stoppage-time equaliser against Bayern Munich in the Champions League final, having come on as a substitute earlier in the game. With seconds of stoppage-time remaining, Ole Gunnar Solskjær scored from Sheringham's headed flick-on, and United won a treble of the Premiership, FA Cup and European Cup with Sheringham – having not won a major honour in his 15-year career on leaving Spurs – now having won every top-level trophy in the English game.
Sheringham's first-team chances remained limited during 1999–2000, but he still played enough times to merit another Premiership title medal. In 2000–01, United secured a third consecutive league title, with Sheringham top-scoring for United and playing some of the best football of his career. In April 2001, he was voted Footballer of the Year by both the Professional Footballers' Association and Football Writers' Association. His fine form ensured that he was still involved with the national side despite being in his 35th year, being named in the squad for the 2002 World Cup.