Twellman returned to the U.S. when he was drafted second overall by the New England Revolution in the 2002 MLS SuperDraft. In Twellman's first season in MLS, he established himself as one of the best players in the league, scoring 23 goals. He finished second in league MVP voting, and was named to the 2002 MLS Best XI. In the 2003 season, despite being beset by a number of injuries, Twellman finished tied with Carlos Ruiz of the L.A. Galaxy for top goalscorer of the league with 15. His production went down in 2004, as he ended up with just nine goals.
After establishing himself in MLS, Twellman made his first appearance with the senior U.S. national team on November 17, 2002 against El Salvador. He struggled to score his first international goal, having several apparent goals waved off for offside infractions. He finally scored against Panama in a World Cup qualifier on October 12, 2005. He improved his chances for a spot on the 2006 World Cup team in a friendly against Norway on January 29, 2006. In the game, he scored the ninth hat trick in U.S. national team history, but was ultimately left off the World Cup roster by coach Bruce Arena.
Taylor's father Tim Twellman, and uncles Mike Twellman and Steve Twellman, all played professionally in the North American Soccer League. Taylor's brother James Twellman played with the San Jose Earthquakes reserves in 2002. Taylor's grandfather, Jim Delsing, was a Major League Baseball outfielder in the 1950s for five teams. His uncle is golfer Jay Delsing.