While at Olympic he turned out for Higher Walton and made guest appearances for Accrington and Vale of Lune, where he suffered knee injuries that threatened his career and forced him to play as a goalkeeper for a time.

Having overcome his injuries, he became a great success as a centre forward and the 1887–88 season saw him finally join Blackburn Rovers, together with his less-talented brother James.

In the FA Cup against Aston Villa Southworth scored four goals as Blackburn registered an 8–1 victory, before going out in the semi-final to Wolverhampton Wanderers.

A contemporary wrote that: "His dodging, his neat passing, his speed and general accuracy in shooting won the hearts of the spectators at the Leamington ground.

[2] Arguably the finest goal-scorer in the Football League during its early years, Southworth scored in all three of his appearances for England.

[citation needed] As Philip Gibbons points out in his book Association Football in Victorian England: "The Blackburn side had given one of the finest exhibitions of attacking football in an FA Cup Final, with England internationals, Walton, Townley, Lofthouse and John Southworth at the peak of their form.

In the opening week of the New Year, Rovers recorded their biggest League win of the season as Combe Hall (4), Southworth (3) and Billy Townley found the net in an 8–0 home success against Derby County.

In the final, played at Kennington Oval on 21 March, Rovers put County under pressure from the beginning and in the 8th minute, centre-half Geordie Dewar scored from a Townley corner.

Jimmy Oswald of Notts County scored a late consolation goal but Blackburn finished comfortable 3–1 winners and won the FA Cup for the fifth time in eight years.

Following his signing from Blackburn Rovers, he replaced the injured Fred Geary, making an immediate impact and soon became a great favourite with the Everton supporters.