O'Ward was born in Monterrey, Mexico, to Patricio O'Ward and Elba Junco, and attended high school in San Antonio, Texas. His surname traces to an Irish great-grandfather. He began karting in 2005 and remained in karts until 2012, before transitioning to open-wheel racing in 2013 across Latam Fórmula 2000, Formula Renault 1.6 NEC, and Pacific F2000. In 2014 he competed in the French F4 Championship. He joined the Pro Mazda Championship with Team Pelfrey in 2015, finishing sixth, then returned in 2016 as championship runner-up.
In 2018 O'Ward signed with Andretti Autosport for the Indy Lights championship. He won nine of seventeen races, was named Rookie of the Year, and clinched the drivers title at the penultimate round in Portland, beating Colton Herta. Two weeks after the championship win, he made his IndyCar debut at Sonoma Raceway for Harding Racing, qualifying fifth and finishing ninth — tying the best debut finish by a Mexican driver in American open-wheel racing.
In 2019 O'Ward joined Carlin on a part-time deal, contesting thirteen races, but failed to qualify for the Indianapolis 500 alongside teammates. He signed to the Red Bull Junior Team in May 2019 and made a one-off Formula 2 appearance at the Red Bull Ring, before Red Bull granted him early release due to FIA Super License point shortfalls, opening the door to a full IndyCar seat.
O'Ward joined Arrow McLaren SP for 2020 and immediately impressed, claiming pole position and his first podium at Road America before finishing fourth in the championship. He won the Indianapolis 500 Rookie of the Year award after finishing sixth in that race.
His breakthrough came in 2021. Racing alongside Felix Rosenqvist, O'Ward won at Texas Motor Speedway — becoming the first Mexican IndyCar winner since Adrian Fernandez in 2004 — and added a second win on the streets of Detroit. He led the championship for a portion of the season before a difficult penultimate race at Portland saw Alex Palou retake the points lead. At the season finale in Long Beach, O'Ward needed to win the race while Palou finished outside the top 13, but he was eliminated in a collision with Ed Jones. He finished third in the championship and claimed the A.J. Foyt Cup as the highest-scoring oval driver.
In 2022 O'Ward signed a three-year contract extension with Arrow McLaren SP. He won at Barber and Iowa, and was runner-up in the 106th Indianapolis 500 after narrowly failing to complete a last-lap pass on Marcus Ericsson. He followed the same pattern in 2024, finishing second at Indianapolis after Josef Newgarden passed him on the final lap. That season also produced three wins: at Mid-Ohio (his first victory under IndyCar's hybrid powertrain era), the Milwaukee Mile, and a retroactively awarded victory at St. Petersburg after Newgarden was penalised for a push-to-pass violation.
In 2025 O'Ward earned his eighth career victory in his hundredth IndyCar start at Iowa, and also won at Toronto.
In 2017 O'Ward competed in the IMSA WeatherTech SportsCar Championship with Performance Tech Motorsports in the Prototype Challenge class. Aged seventeen, he and co-driver James French won the 24 Hours of Daytona and the 12 Hours of Sebring in the PC class — making O'Ward the youngest driver to win both races — and went on to claim the 2017 Prototype Challenge championship and the North American Endurance Cup. In 2022 he shared a DragonSpeed LMP2 car at the Daytona 24 Hours with Colton Herta, Devlin DeFrancesco, and Eric Lux; Herta's late overtake secured the class victory in the final eleven minutes.
McLaren CEO Zak Brown promised O'Ward a test in a current McLaren F1 car if he won at least one IndyCar race. After fulfilling that condition in 2021, O'Ward tested the McLaren MCL35M in Abu Dhabi in December 2021, completing 92 laps and finishing fourth-fastest in the session. Further tests at Barcelona and the Red Bull Ring followed in 2022, and O'Ward made his first Formula One practice appearance at the 2022 Abu Dhabi Grand Prix.
In April 2023 McLaren formally signed O'Ward to their Driver Development Programme, and he has since participated in free practice sessions at the Mexico City Grand Prix in 2024 and 2025 — becoming the first driver to contest an F1 session in his home country in that role — as well as at the Abu Dhabi Grand Prix and the year-end young driver test at Yas Marina in 2025. He continued as McLaren's reserve driver during the 2026 season.