Mavrokefalidis started his professional career with PAOK, after moving to Thessaloniki from Kilkis, where his parents come from. From the first days of his professional career, PAOK head coach Bane Prelević took advantage of his height and decided to play him at the center position, which, as it was proved later in his career, fit him very well. Mavrokefalidis played for PAOK in the Greek Basket League during the Greek League 2005–06 season, averaging 16.7 points and 8.4 rebounds per game. He played in the Greek All-Star Game and he won the Greek League's Most Improved Player Award that year. After many months of hard work, Mavrokefalidis was almost always a member of the starting five in PAOK, creating havoc to the opposition's defense with his ability to get to the rim and make easy buckets or exciting dunks. He also became a defensive force, chasing down rebounds relentlessly, something that can be shown by the 8.4 rebounds per game that he averaged during the 2005–06 season. During the summer of 2006, Mavrokefalidis was signed by Virtus Roma of the Italian League and EuroLeague, but he was not established as a key member of the team, averaging just 2 points and 1 rebound per game. In February 2007, he was transferred from Roma to Pamesa Valencia of the Spanish ACB League, in exchange for Roberto Chiacig and Jon Stefánsson. On July 12, 2007, Mavrokefalidis joined Olympiacos. In 2008, Mavrokefalidis moved to Maroussi. In 2009, he re-signed with Olympiacos through the 2010–11 season. In 2011, Mavrokefalidis was signed by the Russian League club Spartak Saint Petersburg to a 2-year contract worth €2.4 million euros net income. He was named to the All-EuroCup Second Team in 2013. He signed with the Spanish League club FC Barcelona in May 2013. On 10 July 2013, even though the Greek media were saying that Mavrokefalidis was very close to signing with Olympiacos, he was instead announced as a signing of Panathinaikos. In the 2015 Greek Basket League playoffs, he was the best player for Panathinaikos, averaging 18.4 points, 8.1 rebounds, and 2.2 assists per game. On August 10, 2015, he signed a one-year deal with AEK Athens. Mavrokefalidis was the top scorer of AEK Athens in the 2015–16 Greek Basket League season, averaging 14.5 points per game.
On February 20, 2017, Mavrokefalidis returned to the Greek club AEK Athens, signing a contract with them for the rest of the season. On September 25, 2017, Mavrokefalidis signed with Lithuanian club Lietuvos rytas Vilnius, for the 2017–18 season. In 2018, he joined the Greek A2 League club Ionikos Nikaias. On December 23, 2019, after a very productive and successful stint with Ionikos, Mavrokefalidis transferred to the Greek EuroCup club Promitheas Patras, in order to replace Georgios Bogris on the club's roster. Mavrokefalidis signed with Peristeri on July 3, 2020.
A year later, in 2006, the senior men's Greek national basketball team head coach Panagiotis Giannakis became impressed by the Mavrokefalidis' abilities and called him to participate in the Greek basketball senior men's training camp, one month before the 2006 FIBA World Championship took place in Japan. However, as he was selected in the 2006 NBA draft by the Minnesota Timberwolves, Mavrokefalidis informed the coach shortly before the outset of the World Championship that he had decided to go back to Minnesota and participate in performance improvement training camps, and thus he lost the team's 12th man roster place to Sofoklis Schortsanitis. In 2011, Mavrokefalidis was given a 2-month suspension from all competitions by the Hellenic Basketball Federation, for refusing to play for Greece's national team for the second consecutive summer. However, two years later, he played with the Greek senior men's national team at the EuroBasket 2013.
