He played for the Pakistani cricket team in 55 Test matches between 1952 and 1969 and averaged 43.98, with twelve hundreds.

The highest of Hanif's Test centuries was a famous 337 made against West Indies in a six-day test at Bridgetown in 1957. After Pakistan found itself following on from a first-innings deficit of 473 runs on the afternoon of the third day, Hanif spent more than sixteen hours at the crease compiling his runs, allowing Pakistan to draw the game. It remains the longest innings in Test history (and stood as the longest in all first-class cricket for over 40 years). It is the only Test match instance of a triple century in a team's second innings. Displays such as this earned him the nickname "Little Master".

In 1958, he surpassed Don Bradman's record for the highest individual first-class innings. Hanif made 499 before being run out attempting his five hundredth run; this mark stood for more than 35 years before being eclipsed by Brian Lara in 1994.

Many of Hanif's brothers and son were also cricketers: his brothers Mushtaq, Sadiq and Wazir all played Tests for Pakistan, as did his son Shoaib, another brother Raees was once twelfth man for Pakistan, and four nephews had first-class careers.