Zanardi's family moved to Castel Maggiore when he was four years old. His sister Cristina was a promising swimmer before her death in an automobile collision in 1979. Zanardi began racing karts at age 13, building his first kart from dustbin wheels and pipes from his father's work.
He joined the Italian Formula 3 series in 1988, with a fifth-place finish as his best result. In 1989 he secured two pole positions and three podiums despite his team switching to unleaded fuel that reduced engine power. In 1991 Zanardi moved to Formula 3000 with the Il Barone Rampante team, winning his debut race, scoring two more wins that season, and finishing second in the championship.
After testing for the Footwork team, Zanardi was brought in by Eddie Jordan to replace Roberto Moreno for the final three races of the 1991 season; he finished two of them, both in ninth place. In 1992 he had guest drives for Minardi, replacing the injured Christian Fittipaldi. He tested for Benetton in the off-season but contracted with Lotus for 1993. He later reflected that staying at Benetton as a test driver would likely have earned him a full-time seat for 1994 alongside that year's world champion Michael Schumacher.
At the 1993 Brazilian Grand Prix, Zanardi scored his only Formula One point. He was also injured that season when an elderly motorist collided with his bicycle, breaking bones in his foot; he raced in Germany despite the injury. A concussion in a practice crash at the Belgian Grand Prix ended his season early. Zanardi returned in 1994 in the Spanish Grand Prix, replacing the injured Pedro Lamy, but Lotus struggled in its final season and he failed to score points or qualify higher than 13th. For races in Belgium and Portugal he was replaced by Belgian pay driver Philippe Adams. Zanardi later raced sports cars at a Porsche Supercup event at Imola and an endurance race at Donington Park, where he and co-driver Alex Portman retired while leading by over a lap. The pair finished fourth at a rainy Silverstone event.
In 1995 Zanardi went to the United States seeking a drive in the CART Series. Finding no initial interest, Reynard Commercial Director Rick Gorne secured him a test drive at Homestead with Chip Ganassi Racing. Zanardi signed on 23 October 1995; the team's race engineer Mo Nunn had advised against signing him on the basis that Italian drivers were too prone to mistakes. Zanardi rapidly became one of the series' most popular drivers, taking pole in his second race. He won three races in his rookie season and six pole positions, finishing third behind teammate Jimmy Vasser and Michael Andretti, and was named Rookie of the Year.
In the final race of the 1996 season at Mazda Raceway Laguna Seca, Zanardi executed a highly risky overtake on race leader Bryan Herta at the Corkscrew corner — a move subsequently banned for future races — to win the event.
In 1997 Zanardi won five of seventeen races, including three in a row and four of the five rounds in the mid-to-late season, to claim the Drivers' Championship. In 1998, driving a Ganassi Reynard-Honda, he won seven of nineteen races with fifteen podiums in those nineteen races, including four wins in a row in June and July, taking his second consecutive CART title — the third in a row for Ganassi and Honda, and the fourth for Reynard. Zanardi became known as "the Donut King" for spinning his car in tight circles after victories, leaving circular tyre marks on the track; the practice became a widespread celebration across America.
Zanardi's CART success attracted Sir Frank Williams, with whom Zanardi made contact in 1997. He signed a three-year contract with Williams in July 1998, publicly confirmed in September. He began testing alongside test driver Juan Pablo Montoya. Zanardi and the Williams team separated at the end of the season, at an estimated cost of $4 million for the contract termination. Among the season's highlights, Zanardi out-qualified Ralf Schumacher at Monza, qualifying fourth, and overtook David Coulthard and Heinz-Harald Frentzen at the start; a loose floor subsequently forced him to wave rivals past but he finished seventh.
Zanardi tested in July 2000 at Sebring for the Mo Nunn team, driving 246 laps, and signed for the 2001 season. During the 2001 American Memorial at EuroSpeedway Lausitz on 15 September 2001, Zanardi started from the back of the grid. After a late pit stop, while attempting to merge back onto the track he accelerated abruptly, lost control, and spun into the direct path of Patrick Carpentier. Carpentier avoided him, but Alex Tagliani, just behind, could not, and Zanardi's car was struck from behind the front wheel, severing the nose. Zanardi lost both legs — one at and one above the knee — and nearly three-quarters of his blood volume; rapid medical intervention saved his life.
Zanardi was fitted with prosthetic limbs and, dissatisfied with commercially available options, designed and built his own custom legs to compare weight and stiffness for racing use. In 2002 CART honoured him by allowing him to wave the chequered flag in Toronto. Before the 2003 German 500 at the Lausitzring, Zanardi ceremonially drove the thirteen laps he had never finished in 2001; his fastest lap of 37.487 seconds would have qualified him fifth in the actual race.
Zanardi raced at Monza in a round of the 2003 European Touring Car Championship in a car modified for hand-operated controls, finishing seventh. In 2004 he returned full-time with Roberto Ravaglia's BMW Team Italy-Spain in the ETCC. On 24 August 2005 he won his first world-series race in the World Touring Car Championship, celebrating with trademark donuts. He took further wins at Istanbul in 2006 and Brno in 2008 and 2009, and announced his retirement from the WTCC at the end of 2009. He also won the 2005 Italian Superturismo Championship, organised by the Automobile Club d'Italia, with eight victories from twelve races in a BMW 320si run by ROAL Motorsport.
In late November 2006 Zanardi tested a BMW Sauber Formula One car in Valencia, adapted with hand controls on the steering wheel. Since 2004, CRG has produced and sold kart chassis bearing Zanardi's name; Dutch driver Nyck de Vries won the CIK-FIA Karting World Championship in 2010 and 2011 with Zanardi karts. In January 2014 Zanardi returned to motorsport in the Blancpain Sprint Series, racing a BMW Z4 GT3 for Ravaglia's ROAL Motorsport team. In 2018 he made a one-off appearance in the Deutsche Tourenwagen Masters, driving a BMW M4 DTM at Misano; after qualifying last he finished 12th in the first race and fifth in the second in mixed weather. In January 2019 he entered the 24 Hours of Daytona in a GTLM BMW M8 GTE alongside John Edwards, Jesse Krohn, and Chaz Mostert, the team finishing 32nd overall and ninth in the GTLM category.
Following the 2001 accident Zanardi took up handcycling. In 2007 he finished fourth in the New York City Marathon handcycle division after only four weeks of training. He competed at the Para-Cycling Road World Championships in 2009, won the Venice Marathon in the disabled category in 2009 in a time of 1:13:56, won the Rome City Marathon in 2010 in 1:15:53, and in 2011 — at his fourth attempt — won the New York City Marathon in his handcycling class.
At the 2012 London Paralympics, on 5 September, Zanardi won gold in the men's road time trial H4 at Brands Hatch, finishing 27.14 seconds ahead of Nobert Mosandi. Two days later he won the individual H4 road race ahead of Ernst van Dyk and Wim Decleir, and on 8 September took a silver in the mixed team relay H1-4. The bike used was constructed by Italian racecar constructor Dallara. Zanardi was named one of Top Gear's Men of the Year 2012 and voted best male athlete of the 2012 Paralympics.
At the 2016 Rio de Janeiro Paralympics, Zanardi won gold in the H5 road cycling time trial and mixed team relay, and silver in the road race. On 22 September 2018 at a triathlon in Cervia, Italy, he broke the Ironman world record in the disabled category with a time of 8:26:06, also ranking fifth overall.
Zanardi completed the 2014 Ironman World Championship in 9:47:14. He used a handbike for the cycling section and a wheelchair for the running section.
On 19 June 2020, Zanardi was competing in the Obiettivo tricolore Italian national road race for paralympic athletes on State Highway 146 between Pienza and San Quirico. He was descending a hill when he lost control of his handbike and veered into an oncoming truck, sustaining severe facial and cranial trauma. He was airlifted to Santa Maria alle Scotte Hospital in Siena and treated in intensive care. He underwent three hours of neurosurgery and maxillofacial surgery and was placed in a medically induced coma. In September 2020 he was showing signs of interaction; in November 2020 he was transferred to a hospital in Padua, closer to his home. In December 2020 he had regained sight and hearing and could respond non-verbally; in January 2021 he was able to speak again following waking surgery. In December 2021, eighteen months after the accident, he returned home to continue rehabilitation. In July 2022 Zanardi was hospitalised after a fire caused by a defect in his home's solar panels damaged his medical equipment; he was released 76 days later.
Zanardi has been married to Daniela Manni since 1996; they have a son, Niccolò, born 7 September 1998. He co-wrote two books: Alex Zanardi: My Story (2004, with Gianluca Gasparini) and Alex Zanardi: My Sweetest Victory (2004). He wrote the opening chapters of books by former CART medical director Steve Olvey. Awards include the Autosport Gregor Grant Award in 1998 and 2003, the Laureus World Sports Award for Comeback of the Year in 2005, and the Gazzetta Legend Award in 2015. He was inducted into the Motorsports Hall of Fame of America in 2013 and the Long Beach Motorsports Walk of Fame in 2022.
An Alex Zanardi Edition Acura NSX was introduced in 1999 for the US market to commemorate his two consecutive CART championship wins for Honda. Only 51 examples were built, all painted in New Formula Red.
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