He signed for Football League Two side Plymouth Argyle on 30 July 2011 on a free transfer after being released by Ipswich and impressing on trial. He made his professional debut on 6 August 2011, in the opening day draw with Shrewsbury Town at the New Meadow. On 15 October, Hourihane scored his first goal for Plymouth in a 3–2 win over Dagenham & Redbridge. He became the club’s captain during the 2012–13 season following the departure of Darren Purse to Port Vale and signed a new two-year contract in May 2013. Hourihane impressed for Plymouth in the 2013–14 season, starting 53 games and missing only one match all season because of suspension, scoring nine goals in the process.

Hourihane joined Barnsley on 23 June 2014 for a fee of £250,000, signing a three-year contract with the Tykes. He earned the League One Player of the Month award for August 2014, after making an impressive start to his Barnsley career. Hourihane became captain of the club in December 2015.

Hourihane and his teammates won two trophies at Wembley Stadium in London, during the 2015–2016 season: The first visit to Wembley was on 3 April 2016 for the Football League Trophy, in which Barnsley won 3–2 in the League Trophy final, after beating Oxford United of League Two. The second visit to Wembley was on 29 May 2016, for the Football League One play-offs final. Barnsley won promotion to the Championship, after beating Millwall 3–1 in the Play-off final.

Despite speculation linking Hourihane with Aston Villa on 21 January 2017, Hourihane captained Barnsley to a 3–2 victory against Leeds United with Hourihane scoring the match winning goal with a free-kick.

On 26 January 2017, it was confirmed that Hourihane had left Barnsley to sign for Championship rivals Aston Villa for an undisclosed fee. Both Hourihane and Barnsley released a statement, the player thanking the fans and commenting that Barnsley “will always have a special place in my heart”.

On 26 January 2017, Hourihane joined Aston Villa on three-and-a-half-year deal. Hourihane made 17 appearances as Villa finished the season in 13th place, scoring his first Villa goal against Bristol City in February. He scored his first hat trick for the club in a 4–2 victory at home against Norwich City in August 2017.

On 28 March 2017, Hourihane made his senior international debut, starting in a 1–0 friendly defeat against Iceland at the Aviva Stadium. Hourihane won his second cap in a friendly against Mexico on 2 June 2017. On 26 March 2019, Hourihane scored his first senior international goal in a 1–0 win over Georgia at the Aviva Stadium. The Republic of Ireland’s first home match in Euro 2020 qualifying received additional coverage due to a protest against the former CEO of the Football Association of Ireland (FAI), John Delaney. A portion of the Republic of Ireland supporters threw tennis balls on the pitch during the 33rd minute to express their discontent at Delaney remaining part of the FAI hierarchy.

Hourihane signed a new three-year deal in the summer of 2019 as a reward for helping the side win promotion to the Premier League On 5 October 2019, he scored his first Premier League goal in a 5-1 away victory over Norwich City – which meant that he had scored in all four levels of the English football league system.