In October 1996 at the age of sixteen he was brought into the ODI team as a legspinner as a replacement for the injured Mushtaq Ahmed. He then gained notability as a pinch-hitter and began opening with Saeed Anwar. He holds the record for scoring the fastest century in One Day Internationals (off 37 balls) [8], scored in his 2nd match and first ODI innings. He also shares with Brian Lara the record for the third fastest century in ODIs (off 45 balls). One of Pakistan's most useful all-rounders, his extremely aggressive batting style has garnered him over 5000 ODI runs (including a world-record 229 sixes, now broken by Sanath Jayasuriya) as well as taking over 200 ODI wickets and 47 at Test level.

For various reasons, including a perception that he lacks patience in his batting, Afridi had limited opportunity in Test matches. However, Afridi made his presence felt in the third Test against India in March 2005, scoring a quick-fire second-innings half-century and taking five wickets in the match (including Sachin Tendulkar twice) to help Pakistan win the game and register a series draw.

It is perceived that his batting struggles on bouncy pitches and against opponents like Australia, although his record against the Australians has improved over time. Though he has had success as an opener on sub-continent pitches, Afridi is often moved into the lower order as well.