Born in 1978 in the village of Bergentheim, Slot had a modest playing career as an attacking midfielder. He scored 70 goals in 342 league appearances in the top two divisions of the Dutch league between 1995 and 2013. More than half of those appearances were for Zwolle, with whom he began and ended his career. His two other clubs were Sparta Rotterdam and NAC Breda. 

After finishing playing in 2013, Slot moved straight to the coaching staff working with the youth players. After a year he joined second tier Cambuur as assistant head coach, a position he had for two years before becoming interim head coach in October 2016, following the dismissal of Rob Maas. Results improved immediately and the following January Slot was appointed on a permanent basis. He led them from fourteenth to third in the league but missed out on promotion via the play offs. There was also a cup giant killing act against Ajax as Cambuur reached the semi-final for the first time in their history, losing on penalties. 

In the summer of 2017 Slot moved to Eredivisie side AZ67 Alkmaar as assistant head coach. They finished in the top four two seasons running and also lost a cup final to Feyenoord. when head coach John van den Brom moved to Utrecht in 2019, Slot stepped up into the position at AZ67. An impressive campaign was brought to a halt by the Covid 19 pandemic. When the season was suspended AZ67 were second to Ajax on goal difference. Unlike in many other European countries, the season did not resume and no title was awarded. AZ67 lost to Dynamo Kyiv in the Champions League qualifiers but began their Europa League campaign with a 1-0 win away to Napoli. However in December that season, he was sacked by AZ67 when it was revealed that Slot was negotiating with Feyenoord to become their head coach for 2012/22. On leaving AZ67 his points per game ratio of 2.11 was the most of any in the club's history.

In Slot's first season at Feyenoord, they finished third (compared to fifth in 2021).They also reached the Europa Conference League final but were beaten 1-0 by Jose Mourinho's Roma. Slot was voted the Eredivisie manager of the year. The following season, 2022/23, Slot led Feyenoord to their first Eredivisie title since 2017 and only their second of the 21st Century. They also reached the quarter finals of the Europa League and for the second season running Slot was named manager of the year. He was heavily linked to the Tottenham job at the end of the season but opted to stay in Rotterdam, extending his contract to 2026.

Feyenoord had to settle for second place 2023/24 despite accumulating more points than in their title winning season. However, there was success in the Dutch Cup, beating NEC Breda 1-0 in the final. When Klopp announced in January 2024 that he would be leaving Liverpool at the end of the season, Slot's name was not immediately in the frame to replace him. However, when Xabi Alonso announced he would not be leaving Bayer Leverkusen, Slot and Sporting Lisbon's Ruben Amorim became the leading candidates. Liverpool opted for Slot, whose affable personality and ability to develop young players were strong traits. 

Slot said goodbye to the Feyenoord fans on 19 May, the same day Klopp took charge at Anfield for the last time. Despite no official announcement from Liverpool, Slot confirmed beforehand he would be taking over as head coach while Feyenoord's website released a tribute video. At Anfield, Klopp sang Slot's name during his farewell speech, encouraging the Anfield crowd to welcome his successor. The following day Liverpool officially announced that Slot would be head coach from 1 June 2024.

Slot inherited one of the most demanding jobs in world football. Replacing Jürgen Klopp, a manager who had transformed the club and restored it to the summit of English and European football, was viewed by many as an almost impossible task. Yet within twelve months Slot had achieved something few believed possible – he led Liverpool to their 20th league championship and etched his own name into the club’s history.

The Dutchman's first season brought immediate success, but it also saw a noticeable tactical shift from the football associated with Klopp. Liverpool remained an attacking side, yet there was a greater emphasis on structure, control and possession. The high-risk, high-tempo approach that had characterised Klopp's best teams was often replaced by a more measured style designed to minimise mistakes and manage matches.

For much of the campaign the approach proved highly effective. Liverpool built a commanding lead at the top of the table and looked well placed to challenge on multiple fronts, finishing top of the Champions League group stage. From March onwards the side often lacked the intensity and fluency that had marked the opening two-thirds of the campaign. While results remained strong enough to secure the championship, the football was frequently less convincing and several players appeared constrained by the tactical demands placed upon them. Domestically, Slot guided the Reds to the League Cup final, although Newcastle United denied them silverware at Wembley. PSG proved too strong for Liverpool in the last sixteen in Europe. On 27 April 2025, Liverpool sealed the championship with an emphatic victory over Tottenham Hotspur at Anfield. Slot became only the seventh manager in Premier League's history to claim the title in his debut season.

Slot's second season proved far more difficult. Liverpool entered the 2025/26 campaign as reigning Premier League champions but were unable to build upon the success of his debut year despite a bright start, winning the first five league games. The squad that had delivered the club's league title was beginning to change and uncertainty surrounded several senior players. At the season's end long-serving figures Andy Robertson and Mo Salah had both announced that their Liverpool careers were over.

The season was overshadowed by tragedy following the death of Diogo Jota in the summer of 2025. The loss deeply affected the club, its players and supporters. The concerns that had surfaced during the latter stages of the championship-winning campaign became more pronounced. The side often appeared cautious and predictable, lacking the attacking freedom and intensity that had been hallmarks of Klopp's Liverpool. While Slot's emphasis on structure and control had initially delivered results, critics argued that too much of the squad's natural creativity had been sacrificed.

Liverpool secured Champions League qualification, but they rarely looked capable of mounting a sustained challenge for the Premier League crown. The football was frequently unconvincing and the sense of momentum that had accompanied Slot's first season gradually disappeared. By the spring of 2026 it had become increasingly apparent that both manager and club were approaching a crossroads.

When Slot departed Anfield on 30 May 2026, he left behind a mixed but significant legacy. His reign had begun with the daunting task of succeeding Klopp and reached its peak with Liverpool's record-equalling 20th league championship. Yet his final season highlighted the difficulties of sustaining success while attempting to reshape one of the most successful squads in the club's history.