In 1994, when he was 10 years old, Samaras joined his boyhood heroes, OFI Crete. His father was playing for them at the time and then retired in 1996. Six months later, he became Academy chief manager, a position he retained until 2000, when he became manager. Samaras credits his father highly with helping start his football career. His influence meant that Samaras trained every day of his childhood and he also got to spend a lot of time behind the scenes at OFI. Samaras left for Eredivisie club Heerenveen in 2001.

At the start of the 2005–06 season, Sevilla were reported to be interested in Samaras as a replacement for Júlio Baptista. While Arsenal were also looking at him after they had missed out on signing Baptista, some news organisations had reported that Arsenal had already signed Samaras and that he would join at the end of the season. However, the player’s father, Ioannis Samaras said that this was untrue and that his son wanted to stay at the club for another year. Samaras scored on the opening day of the season, on 20 August, when he helped Heerenveen to a 5–4 victory over Roda JC. He picked up a minor leg injury in September, which ruled him out of Heerenveen’s UEFA Cup tie against Baník Ostrava. But he returned to action on 23 September, and scored as Heerenveen beat NEC Nijmegen 2–1. On 14 December, Samaras scored as Heerenveen came back from behind to beat Levski Sofia 2–1 in the UEFA Cup. On 30 December, Samaras scored twice as Heerenveen beat Ajax 4–2. In January 2006, Arsenal and Manchester City showed interest in signing the striker. Samaras tried to get released from his contract after Heerenveen had rejected a bid from Manchester City. However, the Dutch arbitration commission ruled that he had no grounds to end his contract. Samaras scored 25 goals in 88 appearances for Heerenveen.

Samaras moved to Manchester City on 30 January 2006 for a fee of £6 million, a record for a Greek player. He was given the number 20 shirt. Samaras made his debut for City on 1 February, as a 65th-minute replacement for Cole in a 3–0 home win against Newcastle United. His first goal for the club came in the following home match, against Charlton Athletic. The following month Samaras scored in a 2–1 home win against Aston Villa, to put City through to the quarter-finals of the League Cup. This was his fourth goal in six appearances. Samaras scored one further goal that season, in a 2–1 defeat to Tottenham Hotspur.

He made his debut for Greece just a week after his 21st birthday, on 28 February 2006, in a friendly game against Belarus, in which he scored the only goal of the game. He featured in Greece’s Euro 2008 qualifiers and was a member of the unsuccessful Greek squad at the finals, making just one appearance as a second-half substitute in their first UEFA Euro 2008 Group D game against Sweden.

On 29 January 2008, Samaras signed for Scottish Premier League club Celtic on a six-month loan deal, with the club having an option to buy him at the end of his loan spell. He said that he wanted the move because he needed to be playing first team football to get into the Greece squad for Euro 2008. He also said that he was attracted to the fact that he would regularly be able to play in European competition with Celtic.

Samaras was given the number 9 shirt and made his debut on 4 February, in a 5–1 win in the Scottish Cup over Kilmarnock. He scored the final goal of the game after coming on as a substitute. On 20 February, he came on as a substitute in Celtic’s 3–2 defeat to Barcelona, this was his first ever Champions League match. A week later he scored the winner in a 2–1 win over Inverness Caledonian Thistle to help Celtic keep up the pressure on league leaders Rangers. He then scored in Celtic’s next match, a 2–0 win over Hibernian, after coming on as a substitute. Samaras’ next goal came on 23 March, he again came on as a substitute and rounded off the scoring in a 3–0 win over Gretna. On 19 April, he scored the only goal of the game as Celtic beat Aberdeen 1–0, and moved to the top of the league for the first time in 2008. The next month, on 3 May, Samaras again came on as a substitute and scored the winner. His goal gave Celtic a 2–1 victory over Motherwell and kept up Celtic’s late challenge for the league title. Celtic won the title on the last day of the season, 22 May, by beating Dundee United 1–0. Samaras came on as a late substitute and collected his first winners’ medal after the match.

After his successful loan spell, Samaras left Manchester City on 15 July 2008 and signed a three-year contract with Celtic. Although the fee was not disclosed, it was reported to be between £1 million and £3 million. Samaras’ first goals of the 2008–09 season came on 23 August. He scored twice as Celtic beat Falkirk 3–0. On 13 September, he scored another two goals as Celtic beat Motherwell 4–2. He scored twice again in Celtic’s next match as they beat Kilmarnock 3–1. He then scored another two goals as Celtic beat Livingston 4–0 and advanced to the League Cup quarter-final. He was named SPL Player of the Month for September, at this point he was also the top scorer with seven goals.

Samaras began the 2010–11 season in good form, scoring his first goal in a Europa League tie against FC Utrecht with a chest down and finish to make it 2–0, sending Celtic into the second leg with a lead. On 22 September 2010, he scored a hat-trick in a 6–0 win over Inverness Caledonian Thistle in the League Cup. However, the goals then dried up with Samaras failing to score again in 2010.

Samaras’ fourth international goal was a crucial one, when he scored the winning goal in a 2010 World Cup qualifier against Israel in front of his hometown crowd in Heraklion. He scored his fifth international goal with an overhead kick in a World Cup qualifier on 10 October 2009, against Latvia in a 5–2 victory. Samaras also played against Ukraine in a World Cup Qualifying play-off, setting up the only goal of the tie, passing to Dimitris Salpingidis who slotted home to give Greece a 1–0 win and a place in the 2010 World Cup Finals.

On 1 June 2010, Georgios Samaras was selected in the 23-man Greece squad for the World Cup. ESPN.com rated him as Greece’s second best player, only behind talisman Giorgos Karagounis. He played in all three group matches. Despite Greece’s 2–1 win over Nigeria, they failed to proceed to the knockout stage, due to 2–0 losses to both South Korea and Argentina. On 17 November 2010, Samaras scored his sixth international goal in a friendly against Austria in Vienna with Greece winning the match 2–1. Samaras also set up Greece’s second goal.

He then produced a match-winning performance against Rangers at Ibrox on 2 January 2011. He was selected as a lone striker and scored both Celtic goals in a 2–0 victory. His first goal came from latching onto a Joe Ledley pass before rounding Rangers goalkeeper Allan McGregor and slotting home from a wide angle. His second came after he won a penalty which he converted to secure the victory. His efforts in this game won him Goal.com’s World Player of the Week Award. In the following game, a Scottish Cup tie against Berwick Rangers, Samaras again started but failed to last the 90 minutes after sustaining a hamstring injury. Samaras had an influential performance in a 3–0 home victory against Rangers in the SPL on 20 February, helping to set up the second goal for Gary Hooper and causing problems for the opposition throughout the game.

On 16 March, Samaras captained Celtic for the first time in a 2–1 Scottish Cup win over Inverness Caledonian Thistle at the Caledonian Stadium. Two days later, he signed a new deal to keep him at Parkhead until the summer of 2014. Celtic drew 0–0 with Rangers on 24 April 2011 in the final Old Firm league fixture of the season, with Samaras missing a penalty kick late in the second half. The draw kept Rangers one point ahead of Celtic in the league, and the Ibrox club went on to win the league by one point despite Celtic’s emphatic 4–0 win over Motherwell in the final league game of the season (Samaras scoring Celtic’s second goal in that game). Samaras did end the season with silverware though, playing a week later in Celtic’s 3–0 win over Motherwell in the Scottish Cup Final.

On 3 November 2011, Samaras started against Rennes in a Europa League match at Celtic Park. Celtic won the match 3–1 with Samaras getting two assists. He drew plaudits for his much noticed work-rate and determination during the match. Samaras then started the next match against Motherwell in the SPL and set up another goal for Anthony Stokes, Celtic went on to win the match 2–1 after being 1–0 down. Samaras went on to score his first goal of the 2011–12 season in a 5–0 win over St Mirren. Manager Neil Lennon said that; “He got his goal, which we’ve been waiting on a long time. His play was fantastic. He is a talent and all we are asking for is consistency. He has shown everyone today what he is capable of when he is in full flow. The rest took a leaf from his book.” After an impressive performance in Celtic’s 1–1 draw against Italian league leaders Udinese, fellow Serie A side Palermo expressed an interest in Samaras. He had been playing as a left midfielder in the previous few weeks, and the Daily Record said that his good form since returning to the team had helped re-ignite Celtic’s season. On 24 December, Samaras started as a striker and scored twice as Celtic beat Kilmarnock 2–1.

Samaras then went on to score a vital goal for Greece against Croatia on 7 October 2011, a volley from the edge of the box with his left foot. The match finished 2–0 and the result meant that Greece qualified for the Euro 2012. Samaras played in all three of Greece’s group games at Euro 2012, helping them to finish second in Group A and progress to the quarter-finals. He then played in the quarter-final tie against Germany, scoring early in the second half to level the match at 1–1, although Germany went on to win 4–2 and knock Greece out.

Samaras scored an overhead kick in a 2–0 win at Dundee on Boxing Day 2012. In March 2013, Samaras was substituted on as Aberdeen led Celtic 3–1 at Celtic Park, and his overhead kick completed the comeback as he made it 4–3 in the 94th minute of the match.

Samaras started the 2013–14 season with a goal against NIFL Premiership club Cliftonville in the Champions League second qualifying round, and made it two goals in two matches as he scored in the return leg with a header in a 2–0 victory. Celtic won the tie 5–0 on aggregate. Celtic knocked out Elfsborg in the next round, before playing Shakhter Karagandy in the final qualifying round. Trailing 2–0 from the first leg away in Kazakhstan, they rallied in the return match at Parkhead. Samaras scored early in the second half, adding to Commons’ goal just before half time, to level the tie on aggregate. A last minute goal from James Forrest clinched the aggregate win and saw the club once again progress to the group stages. Samaras played in all six group games, but only scored once, away against Barcelona in a 6–1 defeat. He continued to feature regularly in domestic games for Celtic, but was often used as a substitute. He scored a hat-trick on 28 September away against Kilmarnock in a 5–2 win. Samaras only scored another three league goals after that, including a goal from a penalty kick in his final appearance for the club on 11 May 2014, a 3–1 win at home against Dundee United.

On 22 August 2014, Samaras completed a free transfer move to English Premier League side West Bromwich Albion on a two-year contract. He failed to secure a regular place in the team and by January 2015 had made only eight substitute appearances, all without scoring.

On 5 February 2015, Samaras joined Saudi side Al-Hilal on loan for the rest of the season, with an option to sign him permanently at the end of his loan spell. He played against Al-Ahli in the Saudi Crown Prince Cup Final eight days later, but despite scoring his first goal for his new team, they lost 2–1. His next goal came in the first round of the Kings Cup on 10 March 2015, netting his side’s fourth goal in a 4–1 win over Al-Jeel.

On 20 March 2015, Samaras faced a hip injury, the most serious injury in his career that forced him to be out of action for almost three months. In April 2015, Greek newspaper SportDay reported that Samaras was unhappy with life in the Middle East and did not wish to continue his career at the Saudi club when his contract expired at the end of the season. It was also reported that Portuguese club Sporting Lisbon were keen to sign him.

Samaras had his contract with West Brom terminated by mutual consent on 17 July 2015.

In August 2015, Samaras was reported to have agreed terms with Serie A club Sampdoria, but the move fell through as the club were unhappy with the results of his medical. Afterwards, he spent time in New York to rehabilitate from a back injury, and in November 2015 was linked with a move to the New York Cosmos, although once again no move actually materialised.

Samaras did eventually sign for a North American Soccer League team, joining expansion side Rayo OKC on 10 March 2016. On 2 April, he made his debut in their first match, replacing Robbie Findley for the final 12 minutes of a goalless home draw against FC Edmonton. He was the last of three of the team’s players sent off on 28 May in a 1–0 loss at Soccer Bowl holders the Cosmos. Samaras’ first goal for the franchise came on 16 July in his 9th match, coming on as a late substitute to wrap up a 3–0 win over the same opponent at the Miller Stadium.

Samaras became a free agent in early 2017 when Rayo OKC shut down after only one season, and his next move was suggested to be to Spain to sign for Real Zaragoza. On 8 February, he was unveiled at a press conference and assigned the number 5 shirt.

On 6 August 2017, Samaras agreed terms with TFF First League club Samsunspor. On 24 December he scored his first goal with the club, equalizing at the end of the first half, at a 4–2 away loss against Ümraniyespor. It was his first goal since August 7, 2016 when he scored in a draw 1–1 game against New York Cosmos.