Following an unsuccessful trial with Manchester United in 1980, Wegerle chose to play college soccer in the United States. He spent two season with the University of South Florida in 1982 and 1983 and holds the school’s single season scoring record with 21 goals. The Tampa Bay Rowdies of the North American Soccer League drafted Wegerle in the first round of the 1984 NASL college draft. He would play 21 games and score 9 goals, adding 17 assists, during the last year of the NASL’s existence in 1984, being named league’s Rookie of the Year. More significantly, Rodney Marsh coached him at Tampa Bay. This association would be integral to Wegerle’s future move to England. When the league folded, Wegerle moved indoors with the Tacoma Stars of the Major Indoor Soccer League for two seasons. At the University of South Florida, Wegerle came under the professional instruction of ex-Chelsea striker and UEFA Cup Winners’ Cup winner Derek Smethurst, who grounded him and got him ready for his professional career.

In 1986, Marsh, a former Queens Park Rangers star, worked his contacts in England to get Wegerle a tryout. While QPR passed on Wegerle at the time, Chelsea were sufficiently impressed to offer Wegerle a contract. However, Wegerle never played consistently for the Chelsea first team and on March 24, 1988, Chelsea loaned Wegerle to Swindon Town for the last seven games of the season.

At the end of the season, Chelsea sold Wegerle to Luton Town. In his time with Luton, Wegerle became the team’s leading scorer and was sold in December 1989 to Queens Park Rangers for £1 million. He finished the 1990–91 season third on the First Division’s scoring table, including having the honour of receiving the ITV ‘Goal of the Season’ award for that season (against Leeds at Elland Road). Wegerle continued to thrive at QPR until the arrival of new manager Gerry Francis who had little use for Wegerle and sold him in March 1992.

Wegerle gained his US citizenship in 1991, after being eligible through his American wife. He made his national team debut on May 30, 1992 against the Republic of Ireland, and would go on to record 41 caps and score seven goals for his adopted country. On January 8, 1994, Wegerle injured his knee and underwent numerous arthroscopic surgeries, but he was able to recover in time to become a key player for the U.S. in the 1994 FIFA World Cup. By 1998, his repeated injuries had hobbled Wegerle. He enjoyed a brief resurgence leading up to the 1998 FIFA World Cup, but never became the key player he had been in 1994. According to former US National Team Manager Steve Sampson, Wegerle came to him and assistant coach Clive Charles between the February 25, 1998 game at Belgium and the March 14, 1998 match against Paraguay in San Diego and said he had personal knowledge of an affair between US Captain John Harkes and Amy Wynalda, the wife of US Striker Eric Wynalda. As a result, Harkes was dropped from the team. The US would go on to finish in last place at the 1998 FIFA World Cup.

He joined Blackburn Rovers for £1.1 million – a joint record fee to be paid by a Second Division club. He helped Blackburn reach the new FA Premier League as Second Division playoff winners in May 1992, but his first team chances were then dented by the arrival of Alan Shearer at Ewood Park, who led the forward line with Mike Newell.

The 1992–93 season saw yet another transfer for Wegerle as Blackburn sold him to Coventry City in March 1993 for £1 million after only 22 games. Despite a series of injuries, Wegerle played 53 league games for Coventry, scoring nine goals, until his contract expired at the end of the 1994–95 season.

In 1996, Wegerle signed with Major League Soccer (MLS). At the time, the newly established league was signing known players and allocating them to each of the league’s teams in order to ensure an initial parity of talent. As part of this process, MLS allocated Wegerle to the Colorado Rapids. However, he enjoyed little success in MLS.

As a result, Wegerle became part of what is considered the most lop-sided trade in league history, when D.C. sent him to the Tampa Bay Mutiny for Roy Lassiter on April 26, 1998. Lassiter was MLS’s all-time leading goalscorer; Wegerle played the rest of the 1998 season for the Mutiny, scoring a single goal, then retired.