Taylor was raised in St. Louis, Missouri, and attended Saint Louis University High School (SLUH), where he was an all-star athlete in American football, basketball, soccer, and baseball, in which he was offered a contract by the Kansas City Royals. After graduating from SLUH in 1998, Twellman rejected the offer, electing to play soccer at Maryland on an athletic scholarship.

At Maryland, Twellman played soccer in 1998 and 1999; in 1998 Twellman was named a second-team All American for the squad, and in his sophomore 1999 season he finished as a runner-up for both the Hermann Trophy and the MAC Player of the Year Award. After only two seasons with the Terrapins, Twellman left college to turn professional.

In 2000, Twellman signed with German Bundesliga club 1860 Munich. He spent two years with the team, but played for the reserve team in Division III, and never played above the reserve level.

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.

In 2004, Twellman received the inaugural Keough Award, which recognizes the outstanding male soccer player from the St. Louis area.

Twellman’s best MLS season came in 2005, winning both the Major League Soccer MVP Award and MLS Golden Boot, and finishing the regular season with 17 goals. He was also named to the 2005 MLS Best XI. Twellman was the target of transfer talk when Odd Grenland of Norway reportedly made a $1.2 million bid for him, which MLS rejected. In February 2007, New England announced they had signed Twellman to a four-year contract, reportedly worth $5 million.

In 2007, Twellman won his first title with the Revolution: the US Open Cup, a season in which he finished third in MLS in goals scored. The Revolution also won the Eastern Conference title, with Twellman scoring a spectacular bicycle kick against the Chicago Fire to secure the Revs’ spot in the 2007 MLS Cup. Twellman scored the opening goal of the 2007 MLS Cup against Houston Dynamo. However, this would be New England’s only goal as they would go on to lose their third straight MLS Cup by a score of 2–1.

In January 2008, English Championship team Preston North End attempted to entice Major League Soccer and the New England Revolution to sell Twellman. Preston initially advanced an offer of $1.7 million, but MLS and the team rejected that offer, rejected another offer of $2.5 million, and then rejected another bid for $3 to $3.5 million, which would have been the fourth highest and possibly the second highest transfer fee in MLS history to date.

Twellman suffered a neck injury and a subsequent serious concussion from a mid-air collision against Los Angeles Galaxy goalkeeper Steve Cronin on August 30, 2008. Twellman played the rest of the 2008 season, but due to lingering symptoms from his whiplash and concussion, he played only two games in 2009. Twellman had planned to make his return during the 2010 season. However, on June 24, 2010 it was announced that Twellman would not play in the 2010 season and was placed on the season-ending injury list. After struggling to find any playing time over the past three seasons in MLS, due to his head injury, Twellman announced his retirement from the game at the end of the 2010 MLS season.

Twellman has had an active media career after retiring as a player. He’s currently serving as lead analyst for ESPN’s Major League Soccer coverage. He also hosts a weekly recap show about the league, MLS Rewind, on ESPN+. Twellman called the 2012 and 2016 European Championships, and in 2014 Twellman was ESPN’s lead analyst for U.S. matches in the World Cup in Brazil.