Mackenzie hails from Fankerton, near Denny in Stirlingshire, Scotland. He rose through British club racing to establish himself as one of the country's leading road racers of the 1980s and 1990s, winning the British 250cc and 350cc titles twice each during the earlier part of his career before progressing to the world stage.
Mackenzie made his Grand Prix motorcycle racing debut in 1984 in the 250cc class. He stepped up to the premier 500cc class in 1986 aboard a Suzuki, before later riding for Honda and Yamaha. The 1990 season represented his strongest world championship campaign, when he finished fourth in the 500cc championship standings. He finished in the championship's top ten on five other occasions across his Grand Prix career. Mackenzie competed at world level through 1995, accumulating a consistent record that established him as one of the most capable British riders of his generation in the 500cc era.
After his Grand Prix career concluded, Mackenzie returned to domestic British competition and entered the most decorated phase of his career. Riding for the Rob McElnea-run Yamaha team, he won the British Superbike Championship in three successive years: 1996, 1997, and 1998. The hat-trick of titles made him one of the most successful BSB champions of the championship's early years and cemented his reputation as a dominant force on British circuits.
Mackenzie continued competing in British Superbikes until the 2000 season. He made a farewell one-off appearance at Knockhill in 2001, and in 2003 he stood in for the injured Yukio Kagayama at Donington Park — a testament to the regard in which he was still held within the paddock years after his peak.
In 1991, Mackenzie briefly crossed into car racing, driving the celebrity entry at Knockhill in the Honda CRX Challenge. A rain-affected race saw him punted off at the first corner, and a comeback attempt ended when he slid into a tyre barrier at the last corner.
Mackenzie co-owns Mackenzie Hodgson Insurance, works in motorcycling media, and instructs riders on track days across the UK and Europe. He has remained a familiar figure in British motorsport through commentary and paddock involvement.
Mackenzie's personal life produced a second generation of racing talent. His son Tarran Mackenzie won the British Supersport Championship in 2016, the British Superbike Championship in 2021, and graduated to the World Superbike Championship. His son Taylor won the British Superstock 1000cc Championship in 2016 before retiring from competition after the 2021 season. The parallel achievements of Niall's sons in 2016 — both winning British championships in the same year — underscored the family's exceptional depth of racing ability. The Mackenzies stand as one of the few families in British motorcycle racing history to have produced a champion across three generations of competition.