He first appeared for the Reds in the opening pre-season game at Tranmere on 8 July. Matip was a regular for his first season with the Reds, but injury and the arrival of Virgil Van Dijk in January 2018 led to him losing out to Dejan Lovren for the remainder of the campaign. Even though Lovren returned from the Word Cup with an injury, Joe Gomez was preferred to partner Van Dijk for the opening five games of 2018-19. Matip did start the sixth, however, scoring in a 3-0 win over Southampton. Appearances were sporadic and he was ruled out of the Christmas period with a fractured collarbone. However, injuries to Gomez and Lovren allowed him to reclaim the centre-back spot in January 2019 and he retained it for the rest of the season. His passing ability and comfortableness in bringing the ball forward out of defence were key factors in this, and in the Champions League final he teed up Divock Origi for the crucial second goal. Matip's excellent performances for Liverpool were rewarded with a new five-year contract in October 2019.

 

Matip was Van Dijk's partner in the centre of Liverpool defence as the 2019/20 campaign started. A knee injury suffered against Sheffield United on 28 September sidelined him for a month. He returned against Manchester United but suffered an immediate setback and was out for further three months. Matip couldn't reclaim his place from Joe Gomez but was a starter in the goalless draw against Everton when the league resumed after the suspension of season. Matip limped off after a challenge by Richarlison in the second half and missed the final part of the title-winning season. 

2020/21 was another frustrating season for Matip. In the first half of the season he had three different injuries - thigh, back and groin. An ankle injury sustained at Tottenham on 28th January then ended his season, which had been limited to just nine starts. He was back for the start of the 2021/22 campaign and was selected to partner Virgil van Dijk for the season's opening game at Norwich. For most of the campaign he was the preferred partner for van Dijk in the Premier League, but Konate was preferred for the Champions League meaning he was an unused substitute in the final against Real Madrid. In 2022/23 Matip's appearances were limited to just twelve league starts with Konate/van Dijk being Klopp's preferred central defensive pairing. Matip ruptured his ACL during Liverpool's 4-3 win over Fulham at Anfield in early December 2023 which ended his season. He left the club when his contract expired in the summer of 2024 and in October of that year he announced his retirement from the game