[11] He made his senior debut in the 2003–04 season as a substitute against Hibernian on 24 April 2004,[12] but still continued to play for the under-19s side, with whom he won the Scottish Youth Cup, beating Rangers 1–0 at Rugby Park.

[16] He signed a new four-year contract extension,[17] and went on to win the Scottish Football Writers'Young Player of the Year award, after scoring twelve goals during the season.

On 31 August 2007, Kilmarnock accepted Rangers' offer for Naismith for around £1.9 million[25] and he joined the club just 19 seconds before the transfer window closed.

[27] Naismith made his Champions League debut at the Camp Nou against FC Barcelona in November 2007, coming on as a 78th-minute substitute.

[37] Naismith featured in the 2009 Scottish Cup Final win over Falkirk after missing the majority of the season through injury.

[41] The following week, he was deployed as a lone striker in a Champions League Group stage fixture against Sevilla at Ibrox and was unfortunate not to be awarded a penalty in the first half of an eventual 4–1 defeat.

On 29 September 2010, Naismith scored the only goal of the game as Rangers defeated Bursaspor at Ibrox to gain them their first win in 12 UEFA Champions League matches.

[55] After the new year, Naismith scored the winning goal in the Scottish League Cup semi final against Motherwell at Hampden Park.

[77] Naismith signed a four-year deal for Everton on 4 July 2012,[78] joining his previous striking partner at Rangers, Nikica Jelavić.

[79] The nature of the move, described by Naismith as "one of the hardest decisions" of his football career,[80] required FIFA to grant provisional international clearance, which allowed him to play in England while arbitration over the movement of assets out of Rangers continued.

[81] He made his debut for the Toffees as an 89th-minute substitute during Everton's first match of the season, a 1–0 league victory over Manchester United.

[87] Later in the 2013–14 season, Naismith embarked on a good run of form that coincided with Everton winning seven league matches in a row, culminating with a pair of man-of-the-match performances against both Fulham and Arsenal.

[89] Naismith scored goals in each of the first three games in the 2014–15 Premier League season, against Leicester City,[90] Arsenal[91] and Chelsea.

[92] On 6 November 2014, he scored his first European goal for Everton in a 3–0 UEFA Europa League group stage win against Lille.

[100] On 18 January 2018, Naismith joined Scottish Premiership side Heart of Midlothian on loan until the end of the 2017–18 season.

[101] He made his debut[102] for Hearts on 21 January 2018, playing from the start in a 1–0 win over Edinburgh Derby rivals Hibernian at Tynecastle Park, in the Fourth round of the Scottish Cup.

[103] He scored the winning goal against Hibs in a home league fixture on 9 May with a flicked header, but the following day was banned by the SFA for two matches (with only one round remaining in the season) for a challenge on Celtic's Scott Brown the previous week.

[110] At the end of the 2020–21 season, after helping the team win promotion back to the Premiership, Naismith announced his retirement from playing at the age of 34.

[116] Naismith was called up to the Scotland squad for the first time in June 2007, for a friendly away to the Faroe Islands; he came on as a substitute for Kris Boyd for the final seven minutes of a 2–0 win on the 6th.

[118][119] He was selected for all three of Scotland's matches in the 2011 Nations Cup when they reached the final but were defeated by the hosts Republic of Ireland.

[124] Craig Levein was known to utilise Naismith for his attacking instincts, workrate and sense of responsibility during his tenure as Scotland manager.

[125] Naismith was appointed on a permanent basis in June 2023, but was given the job title of technical director as he had not yet achieved the required UEFA coaching licences in order to represent the club in European competition (this role was taken by Frankie McAvoy).

[126] In September 2023, a week after Hearts had been eliminated from the Europa Conference League, Naismith was made head coach and McAvoy his assistant.

[128] Hearts were sat bottom of the Scottish Premiership with only a single point gained from their first six matches, and having lost their prior eight games in a row in all competitions.

[130][131] In August 2014, he donated tickets for Everton matches to be distributed via Liverpool jobcentres to unemployed people actively looking for work.