When Borini signed a contract to join Liverpool in the middle of July 2012, the Reds became the third English club he had been on the books of even at the early age of 21. He was, however, a footballer already well known by the manager who signed him for Liverpool because Brendan Rogers had been Swansea’s manager when the Italian was loaned to the Welsh club by Chelsea for the closing weeks of the 2010/11 season. Liverpool’s new boss explained why he was so keen to complete this signing: “Fabio fits the model of what we're trying to do in building not only for now, but also for the future. He's a big talent, 21 years of age, he scores goals, and his passion, focus and concentration is a very important part of his game. I think the supporters will love him. He's a multi-functional player who can play in a number of positions and someone I believe has got great growth. He is arguably the best physical player I've worked with in terms of his pace, power and fitness. Mentally, he's very strong.”

After scoring ten goals in eleven matches for Chelsea reserves in the 2008/09 season he played in eight first-team games for the West London team. Although Borini performed well under Rogers at Swansea with six goals in nine Championship matches and was a member of the team that secured City’s place in the Premier League, he issued a statement saying that he would not be returning to Chelsea after his loan-period with Swansea as he had reached an agreement to sign for Parma. But less than two months after signing for Parma, he moved on to Roma, initially on loan but with the club from the capital having an option to make the deal permanent later. Borini was not given much of a chance in the first half of the season at Roma but once he got going there was no stopping him, his best run being ten goals in 14 matches from 26 October 2011 to 10 March 2012. The loan was upgraded to a co-ownership deal and in the summer of 2012 Roma outbid Parma in a blind auction parting with £4.3 million to secure the other 50% of his registration.

Like many strikers Fabio Borini has his own special way of celebrating a goal he has scored. His trademark of drawing his hand across his mouth to signify a dagger between his teeth comes from an Italian saying. The man himself explains: “When you want to achieve something so badly that you are angry to achieve your goals, you put the knife between your teeth. That’s what I was trying to do by putting the side of my hand in my mouth.” Borini was in Italy’s 23-man Euro 2012 squad but was one of only two outfield players not to see any action. After a short break following the end of the championships, he was able to join up with his new teammates on Liverpool’s North American tour. He can play on either the left and right flank as well as up front and will deliver steely determination to Liverpool's cause serving as a direct replacement for Dirk Kuyt who departed to Turkey. Liverpool supporters saw his ‘dagger celebration’ as early as in his home debut, against Gomel in the Europa League, but Borini's hopes were dashed when he broke a bone in his foot and was sidelined until January 2013. "It was extremely frustrating because in the last three years I have got injured for three months every year in October. I haven't played a full season yet because of those injuries, but I hope they'll stop. It's just been bad luck and nothing about me. They've been different injuries each time."

Borini missed the majority of his first season as a Liverpool player because of injury. Almost as soon as he had recovered from the broken foot he received against Manchester United in September, he was further sidelined by a dislocated shoulder against Swansea in February that was expected to keep him out for the remainder of the season. He recovered to play at Newcastle on the last weekend of April and scored his first Premier League goal and the team's fifth in a 6-0 rout. Considered surplus to requirements at Liverpool during the summer of 2013, Borini was sent on a season-long loan to Sunderland where he became a real crowd-favourite, so much so that he was given the club's "Young Player of the Year" award. He endeared himself to his new fan-base by scoring the winning goal in the Tyne-Wear derby against Newcastle United at the end of October. He added six more Premier League goals by the end of the season, including the  goal that ended Jose Mourinho's long unbeaten run at Stamford Bridge in the league. Borini was also prominent in the League Cup, scoring against Chelsea in the 5th round and against Manchester United in the first leg of the semi-final at the Stadium of Light. He also opened the scoring in the Wembley final against Manchester City but City recovered to win the trophy by three goals to one. Once seven points adrift of safety, Sunderland recovered to retain their Premier League status and Borini certainly played a big part in that.  

Borini decided to remain as a Liverpool player in the summer of 2014 despite the club accepting an offer from Sunderland, with whom the Italian had enjoyed a successful loan-spell in 2013/14. The forward only started in five matches, scoring just once in the away win at Aston Villa in the middle of January. With two years left on his Liverpool contract Sunderland finally got their man on the last day of the August transfer window in 2015. Although he struggled with injury during the season, he made 22 starts in the league and scored some crucial goals towards the end of the campaign as Sunderland avoided relegation at the expense of rivals Newcastle. He remained at Sunderland for 2016-17 but following their relegation he was loaned to AC Milan for 2017-18. His performance convinced Milan to sign him permanently on 1 July 2018.