In 2011, his family moved from Hyderabad to Bangalore, where he began training at the Karnataka Institute of Cricket. Starting from 2014, he represented Karnataka in under-16 and under-19 age categories. His domestic debut for Karnataka in the 2018-19 Ranji Trophy. He performed consistently, scoring crucial runs and this success caught the eye of the Royal Challengers Bangalore (RCB) franchise in the Indian Premier League (IPL). He became the first player in IPL history to score three fifties in his first four matches.

Padikkal made his List A  debut for Karnataka in the 2019-20 Vijay Hazare Trophy. He was the leading run-scorer in the tournament, with 609 runs in eleven matches.

In 2019, he was named in India A’s squad for the 2019-2020 Deodhar Trophy. He made his Twenty20 debut on 8 November 2019. For Karnataka in the 2019-20 Syed Mushtaq Ali Trophy.

In the 2020 IPL auction, RCB acquired Padikkal, recognizing his potential as a future star. This opportunity to play alongside established players like Virat Kohli and AB de Villiers provided him with valuable experience.

In 2021, Padikkal received his maiden call-up to the Indian team for a limited-overs series against Sri Lanka. In 2024, he was added to India’s Test squad for their series against England as a replacement for KL Rahul. He made his Test debut in 2024 and scored 65 runs off 103 balls.

Padikkal won the Emerging Player Award for the 2020 Indian Premier League playing for Royal Challengers Bangalore. He scored 473 runs in 15 matches for RCB in his debut IPL season. He was selected in Karnataka’s squad for the 2021 Syed Mushtaq Ali Trophy. On April in the 2021 Indian Premier League, Devdutt scored his maiden hundred with a score of 101, as RCB beat the Rajasthan Royals by ten wickets.

In February 2022, he was bought by the Rajasthan Royals in the auction for the 2022 Indian Premier League tournament. In March 2022, Padikkal scored his maiden first-class century with 178 runs in the 2021-22 Ranji Trophy match against Puducherry. In April 2022, while playing for the Rajasthan Royals, he scored his 1,000 runs in the IPL. In November 2023, he was traded to Lucknow Super Giants ahead of the 2024 season.