Born in Wollongong, New South Wales, Gardner began racing in 1977 at age 18 on a second-hand Yamaha TZ250 in the Australian championship, finishing second on debut at Amaroo Park before recording his first win weeks later at Oran Park Raceway. He came to international attention when Mamoru Moriwaki hired him for the Australian Superbike championship in 1981. At that year's prestigious Suzuka 8 Hours, Gardner and co-rider John Pace qualified the Moriwaki Kawasaki on pole position ahead of all major factory teams.
Fellow racer Graeme Crosby — contracted to Suzuki — personally sponsored Gardner to race in the British Superbike Championship on Kawasakis run through the British Moriwaki operation. Gardner won his first race in England and contended for the title before a late-season engine misfire relegated him to third overall. His results earned him a contract with Honda Britain.
Gardner's Grand Prix debut came at the 1983 Dutch TT, where he was involved in a serious incident with reigning world champion Franco Uncini. Uncini fell as he exited a corner and was struck by Gardner's bike, going into a coma before ultimately recovering. Gardner scored no points in his two 1983 outings. In 1984 he won the British 500cc national championship and contested five world championship races, including a third-place finish at the Swedish Grand Prix.
Gardner received full Honda factory support for 1986 alongside Freddie Spencer. He won his first Grand Prix at the Spanish Grand Prix, claimed two further victories, and finished second in the championship behind Eddie Lawson.
The 1987 season brought Gardner his world championship, winning seven of sixteen races and wrapping up the title with a victory in the penultimate round in Brazil at Goiania — the first Australian to win the premier class title. His race engineer that year was fellow Australian Jeremy Burgess, who had previously worked with 1985 World Champion Freddie Spencer and would later become the long-time engineer of Valentino Rossi.
In 1988, defending champion Gardner was hampered by an NSR500 that was difficult to ride. He still took four victories — in the Netherlands, Belgium, Yugoslavia, and Czechoslovakia — but finished second overall behind Eddie Lawson on the Marlboro Yamaha. A mechanical failure at Paul Ricard while leading with less than a third of a lap remaining cost him a certain race win.
Gardner's 1987 championship had a transformative effect on motorcycle racing's profile in Australia, helping catalyse the inaugural Australian Motorcycle Grand Prix at Phillip Island in 1989. Gardner delivered the home crowd a memorable win at the first running of the event, edging Wayne Rainey and Christian Sarron. That season ended on a painful note when a crash at Laguna Seca broke his leg and ended his year early. He also won the Suzuka 8 Hours four times: 1985, 1986, 1991, and 1992.
In 1990, Gardner won at Jerez but missed three rounds through injury, finishing fifth in the championship. He closed the season with a second consecutive Australian Grand Prix win at Phillip Island, this time from teammate Mick Doohan. Gardner retired from motorcycle racing after the 1992 season.
Gardner's transition to four-wheel motorsport began tentatively in 1990 with a Formula Holden appearance at the Australian Drivers' Championship supporting the Australian Formula One Grand Prix. He then drove a Holden Commodore at the 1992 Bathurst 1000, and contested four events in the German DTM that year in a Jagermeister-sponsored BMW E30 M3 Sport Evolution.
In 1993, Gardner joined the Holden Racing Team for the Australian Touring Car Championship's first season in the new 5.0-litre format. A number of on-track incidents earned him the nickname Captain Chaos, and he was briefly suspended from the team for the Sandown 500, though his simultaneous discussions with sponsors about forming his own team were the underlying cause.
For 1994, Gardner formed Wayne Gardner Racing, backed by Coca-Cola, and raced for three seasons alongside television commentator Neil Crompton. The team's most prominent result came at the 1995 Tooheys 1000, where Gardner and Crompton finished third. Gardner won the 1997 Calder Park round — a surprise result given the team's financial uncertainties that season. When Coca-Cola redirected its sponsorship budget toward the 2000 Sydney Olympics, the team lost an estimated two million dollars per year and folded after a partial 1999 campaign. Gardner continued racing V8 Supercars until 2002, including taking pole position for the 2000 Bathurst 1000 in difficult wet conditions.
Gardner also competed in the All Japan Grand Touring Car Championship in a works Toyota Supra from 1996 to 2002, winning rounds at Fuji Speedway in 1999 and Sportsland SUGO in 2001. He made a one-off appearance at the 1998 24 Hours of Le Mans in a Riley and Scott alongside Philippe Gache and Didier de Radiguès, qualifying 26th but retiring with engine problems after 155 laps.
Following his 1987 championship, Gardner was appointed a Member of the Order of Australia in the 1988 Birthday Honours for services to motorcycle racing. He was inducted into the Sport Australia Hall of Fame in 1991 and received an Australian Sports Medal in 2000. The FIM honoured him as a MotoGP Legend. The Gardner Straight at Phillip Island Grand Prix Circuit stands as the most visible commemoration of his impact on Australian motorsport.
Both of his sons, Remy and Luca Gardner, have competed professionally in motorcycle racing, continuing a family thread that stretches across decades of the sport.