On 22 December 2006, the club directors offered him a five-year contract and just two weeks after that day, on 7 January 2007, Panathinaikos coach Víctor Muñoz selected him in the main squad for the match against Egaleo at the Olympic Stadium.

He became the second youngest player ever to wear the club's shirt in a league match, at the age of sixteen (the first was Kostas Antoniou − 15-years old – in 1978).

On 15 February 2007, Ninis became the youngest player to participate with a Greek football team in a European cup match, against Lens in France.

He repaid this faith through his performances against teams such as Charleroi Having entered the pitch at half-time, Ninis assisted three goals and scored one, aiding Panathiniakos to a 5–1 victory against the Belgian club.

On 11 August 2008, it was revealed that ten Cate had selected Ninis to be one of the new captains of Panathinaikos, along with fellow players Dimitris Salpingidis and Gilberto Silva.

In February 2010, Ninis made his best appearances with Panathinaikos and generally in his personal career so far in the knockout stage of the UEFA Europa League against AS Roma.

[2] On 20 May 2012, he played his last match with Panathinaikos in the 2011–12 Superleague Greece playoffs final against AEK and was replaced by substitute Giorgos Karagounis in the 70th minute.

[8] On 10 September 2017, Ninis signed for one year at Maccabi Petah Tikva of the Israeli Premier League as a free agent, after being released from KV Mechelen a week earlier.

Ninis returned to duty for the Under-19 Elite qualifying round of the European Championships, after making his senior international debut.

Ninis, who impressed as Greece reached the final of last year's UEFA European Under-19 Championship, expressed his delight at the news, saying: "It's a dream come true and an extra motivation to work even harder and improve myself.

On his debut Ninis scored the opening goal of the games versus Cyprus in the fifth minute, after a solid pass by Dimitris Salpingidis, Ninis slotted the ball underneath Antonis Georgallides and into the back of the net making the perfect debut and start for his country and becoming the youngest ever scorer for Greece with 18 years and 46 days, breaking Kostas Eleftherakis' old record by 244 days.

On 1 June 2010, Otto Rehhagel named his official 23-man squad for the 2010 FIFA World Cup in South Africa.

On 2 September 2011, Ninis scored the winning goal in a qualifying match for the UEFA Euro 2012 against Israel, in Tel Aviv.