Ponikarovsky began his professional hockey career by playing for the Dynamo Moscow, one of the premier clubs in Russia. He played for Dynamo 2 and Dynamo Jr., farm teams of Moscow, between 1995 and 1999. In 1997-98, Alexei played 24 games for Moscow Dynamo in the First Division of the Russian Hockey League, collecting three points with 30 penalty minutes. He then played 13 games for Krylya Sovetov of the Russian Elite League in 1998-99 and played three playoff games for Moscow Dynamo. Ponikarovsky was a member of Moscow during the 1998-99 season, but saw little playing time. He finally become a full-time playing member of the main team during the 1999-2000 season. Alexei played 19 games for Moscow Dynamo of the Russian Elite League and played 29 games for THK Tver in the First Division of the Russian Hockey League collecting 22 points (eight goals, 14 assists) with 26 penalty minutes. Ponikarovsky's main time was spent with Dynamo, as the team ended up winning the Russian Super League Championship with Moscow.
Ponikarovsky was drafted in the fourth round, 87th overall by the Maple Leafs in the 1998 entry draft. He made his NHL debut in the 2000-2001 season, playing 22 games with the Maple Leafs, scoring one goal and four points. His breakout NHL season did not come until the 2005-2006 season, where Ponikarovsky put up career highs in goals, assists. points, and penalty minutes. He saw added responsibility and was given more ice-time, often with former Moscow Dynamo teammate Nik Antropov or Mats Sundin, and became one of the team's regular penalty-killers. Ponikarovsky finished the season with four shorthanded goals and one shorthanded assist. His four shorthanded goals tied ten players, including teammate Matt Stajan, for eighth in the league.
On December 16, 2006, Ponikarovsky scored a career high five points in Toronto's 9-2 victory over the New York Rangers, scoring two goals and assisting on three others. He is commonly referred to by his teammates as "The Poni Express" , "The Ukraine Train" or simply "Poni". On May 10, 2007, the Maple Leafs re-signed Ponikarovsky to a three-year, $6.315 million contract.