Zabel grew up in East Berlin, in the borough Marzahn. His father Detlev was a professional cyclist. His first international success as a junior was at the track world championship when he was third in the team pursuit on the East German team. In 1988 he was fifth in the points race. In 1989, as a 19-year-old, he was included in the East German national track team for professionals. That year he became national champion of East Germany in the individual pursuit.
After the Fall of the Berlin Wall he moved to Dortmund and became part of the amateur team RC Olympia Dortmund, led by Hennes Junkermann. He was second at the first national road championship of re-unified Germany in 1991, first at the regional championship of North Rhine-Westphalia and was included in the amateur German team for the World Championship in August. In 1992 he made name as a strong sprinter, winning the green jersey in the Peace Race and taking several stage wins in stage races. In July he was fourth in the road race of the 1992 Olympic Games in Barcelona, where he won the sprint of the peloton.
In late 1992 he turned professional with the small German team Union-Frondenberg, before changing in 1993 to Team Telekom where he further developed as a sprinter. On 27 April 1994 Zabel tested positive for clostebol metabolites in Veenendaal-Veenendaal. He was fined 3000 Swiss francs and lost 50 points. A suspension on probation was cancelled. Later that year he won Paris–Tours in a mass sprint, his first win in a classic race.
In 1995 he won two stages on the Tour de France, his first success on a grand tour.
In 1996 he won again two stages in the Tour de France and won the points classification. He took over the green jersey in the 10th stage and wore it until the end of the Tour. That year his Telekom team took first and second place in the general classification as well, with Bjarne Riis and Jan Ullrich respectively.
In 1997 Zabel won his first monument classic, Milan–San Remo. He was the only sprinter in a group of forty to make it to the finish and easily won the sprint. Later that year, he won three stages on the Tour de France and secured his second green jersey.
In 1998 he won Milan–San Remo a second time and became national road champion of Germany. He won his third green jersey in the Tour de France, however this time without a stage victory.
In 1999 he was second in Milan–San Remo, winning the peloton sprint behind Andrei Tchmil who had broken clear in the final kilometer and managed to maintain his effort. He won the important German semi-classic Rund um den Henninger Turm in Frankfurt and won his fourth consecutive green jersey, equalling Sean Kelly's record, again without winning a stage.
In 2000 he won two legs of the UCI Road World Cup in spring: Milan–San Remo a third time and a surprise win in the Amstel Gold Race, beating Michael Boogerd in a bunch sprint. In the summer he won an unprecedented fifth green jersey, thereby surpassing Kelly's previous record. At the end of the year, he was the best overall in the World Cup and number two on UCI World Ranking.
In 2001 he won Milan-Sanremo a fourth time, the most since cycling legend Eddy Merckx, earning him the nickname Signore Milano-Sanremo in Italy. He won the points classification in the Tour de France a sixth consecutive time, winning three stages furthermore. Zabel's unique streak of six green jerseys was owed to his all-round ability: he was one of the strongest sprinters, but could also climb reasonably well. This meant that, apart from taking the maillot jaune in the Tour de France thanks to time bonuses, he could pick up further victories when other sprinters had retired and take the maillot vert to Paris. One memorable victory in securing the green jersey was in the 2001 Tour de France, when his competition with Australian Stuart O'Grady lasted from the first week until the final stage in Paris, where Zabel's better placing took the green jersey off O'Grady's shoulders. Later that summer, he also won the HEW Cyclassics, Germany's biggest one-day classic, and his seventh World Cup race. In September he won three stages, consecutive, in the Vuelta a España and was fifth in the World Championship road race in Lisbon.
2001 turned out to be his most successful year ever. At the end of the year, he had won 29 races and was number one on the closing standings of the world ranking.
In 2002 he missed the breakaway in Milan–San Remo but won Rund um den Henninger Turm a second time. In the summer, he failed to win a seventh consecutive green jersey in the Tour de France. He won one stage victory, his twelfth in total, but was ultimately beaten by Australian Robbie McEwen in the final points classification. He won the points classification in the Vuelta a España instead, without winning a stage. In Zolder, in Belgium, he finished third at the World championship in a peloton sprint behind Mario Cipollini and Robbie McEwen. At the end of the year, he maintained his number one position on the world ranking.
In 2003 he became national road champion of Germany for a second time, but failed to win a stage in the Tour de France and was third in the final points classification. He won two stages in the Vuelta and again won the points classification of the race. In October he won Paris–Tours for the second time in his career and was awarded the unofficial Ruban Jaune for winning the race in a record average speed for a one-day race of 47.55 km per hour. The record stood until 2010 when Óscar Freire won Paris–Tours riding at an average of speed of 47.73 km per hour. He ended the year as number two on the world ranking behind Paolo Bettini.
In 2004 Zabel began the season losing what would have been his fifth Milan–San Remo. He looked secure to win the sprint, but lifted his arms to celebrate too early and was ultimately foiled by Óscar Freire. He was third in the points classification of the Tour de France and first in the Vuelta points classification, but despite numerous second and third places, he didn't win a stage. His first place in the Vuelta was also his ninth win in a points classification of a grand tour, an all-time record. At the 2004 Olympics in Athens, he was again fourth in the road race, again winning the sprint behind three escapees and so missing an olympic medal twelve years after Barcelona. In October, after 9 victories and 18 second places throughout the season, he ended the year as he had begun it: second behind Freire, this time in the world championship in Verona.
In 2005 Zabel became the first to win Rund um den Henninger-Turm in Frankfurt a third time, in his first win on the season. In May he participated for the first time in his career in the Giro d’Italia, seeking the only points classification he had not yet won, but failed to win a stage and was sixth in the points ranking. His Telekom Team, keen on winning the Tour de France with Jan Ullrich, decided not to include him in the selection for that year's Tour, much to the discontent of Zabel, who declared at the start of the HEW Cyclassics that he would be leaving the team at the end of the year. He rode the Vuelta, but was unable to win a stage or the points classification despite multiple second places behind Alessandro Petacchi, and played no role in the World Championship in Madrid. In October he won Paris–Tours a third time, equalling the record in the classic of Gustave Danneels, Paul Maye and Guido Reybroeck.
At 35, Zabel left his team Telekom after 13 years, and signed on for the Italian-German team Milram in 2006, where he teamed up with Alessandro Petacchi. Petacchi was considered the fastest sprinter in the world by then and would focus on an Italian program, but the Italian broke his knee in the Giro, making Zabel the leader of the team that season. He had to wait until 24 May to take his first win of the season, a stage in the Bayern Rundfahrt. In the Tour, he was the team leader in the absence of a GC contender, and was ultimately second in the points classification, but his best stage results were two third places. In the Vuelta he won two stages, his first ProTour wins in 2006, before heading to the world championship. In Salzburg, he finished second in a three-man sprint with Paolo Bettini and Alejandro Valverde, his third podium finish in the world championships.
In 2007 he won two stages in the Bayern Rundfahrt and one in the Tour de Suisse. He was again captain in the team selection for the Tour de France, after Alessandro Petacchi had been suspended for a positive salbutamol test. He wore the green jersey one day, was twice second and once third in a stage, but was third once more in the final points classification. In July he won one stage in the Deutschland Tour, his 13th in total, and won the race's points classification for the seventh time. In September he won the seventh stage in the Tour of Spain, ahead of world champion Bettini, totalling eight stage victories in the Vuelta throughout his career.
In 2008 he won one race, a stage win in the Tour of Valencia early in the season. In his last participation in the Tour de France, at age 38, he was once more third in the final points classification. In September 2008 Zabel stated he would retire the following month after 16 years as a professional cyclist with 209 professional road victories and many more podium finishes. In December 2008 he joined the Columbia team as an advisor, to work alongside riders such as Mark Cavendish, André Greipel and Mark Renshaw.
On 24 May 2007 Zabel and former Team Telekom team-mate Rolf Aldag admitted using EPO to prepare for the 1996 Tour de France. Zabel told at a press conference he experimented with it for a week and stopped due to side effects. He apologized for lying about using EPO in the past. His confession was triggered by accusations by former Team Telekom masseur Jef d'Hont and the confessions of Bert Dietz, Udo Bölts and Christian Henn, all former members of Team Telekom. D'Hont's book, of which excerpts were printed in the German political magazine Der Spiegel in April 2007, accused members of Team Telekom of systematic doping with EPO in the mid-1990s.
His name was also on the list of doping tests published by the French Senate on 24 July 2013 that were collected during the 1998 Tour de France and found positive for EPO when retested in 2004. As a result of this report, Zabel admitted to doping from 1996 to 2004. Also as a result Zabel was suspended from his coaching role with Team Katusha and resigned his membership of the UCI's Professional Cycling Council.
In July 2013 Zabel finally admitted to sueddeutsche.de and revealed the level of his truth-bending. He told the German publication that he actually used the substance between 1996 and 2003, as well as other banned products and methods. "EPO, cortisone, then even blood doping: it is still a big deal," he said.
As of February 2007, Zabel had 192 victories as a professional, more than any other active rider.