Selected by the Nashville Predators in the first round (No. 15) of the 2004 NHL Draft, Radulov raised expectations following two successful seasons with Quebec of the Quebec Major Junior Hockey League.

The Russia-born forward had 75 points (32 goals, 43 assists) in 65 games in 2004-05, then followed that with a team-record 152 points (61 goals, 91 assists). He tied a team record by scoring six goals in a game against Drummondville in October 2005, then topped it in March 2006 when he had seven goals and 11 points against Rimouski.

Radulov also had 55 postseason points (21 goals, 34 assists) in 2006, including three goals and two assists against Moncton in the Memorial Cup championship game, and was named tournament MVP after Quebec's 6-2 win.

The Predators brought him to the NHL early in the 2006-07 season, and he had 37 points (18 goals, 19 assists) as a rookie. Radulov improved to 58 points (26 goals, 32 assists) in 2007-08, then jumped to the Kontinental Hockey League, signing a three-year contract with Salavat while still under contract with Nashville.

He returned to play nine regular-season games and eight Stanley Cup Playoff games with the Predators in 2011-12 but was not offered a contract by Nashville and went back to the KHL, playing the next four seasons with CSKA Moscow. He finished first or second in the KHL scoring race in three of the four seasons.

Radulov returned to the NHL in July 2016, signing a one-year contract with the Montreal Canadiens. He scored 54 points (18 goals, 36 assists) 76 games in 2016-17, then became a free agent and signed a five-year contract with the Dallas Stars.

On Jan. 1, 2020, Radulov scored the go-ahead, power-play goal during the Stars' 4-2 victory against the Predators in the 2020 Bridgestone NHL Winter Classic at Cotton Bowl Stadium in Dallas. He scored eight goals, including four game-winners, and 18 points in 27 games during the Stars' run to the 2020 Stanley Cup Final.