Misbah would eventually make his first-class debut in 1998, aged 24 for Sargodha. Misbah went on to be selected for the Pakistani Test side in 2001 and the ODI cricket team in 2002. Misbah married Uzma Khan in 2004. The couple have two children.

Although making his international debut back in 2001, his breakthrough came when was selected for ICC World T20. Misbah was influential in his prolific 2007 ICC World Twenty20 famously playing the Paddle Scoop in the Final against India in the final over as Pakistan lost by 5 runs. He was leading run scorer from Pakistan and third overall in the tournament. Also he was the first Pakistani player who reached No. 1 position in ICC T20I batsmen rankings. He was also the first Pakistani player to score a 50 in T20I. His knock of 66 against Australia was named as the fourth-best T20I batting performance of the year by ESPNCricinfo voters. He was named in the ‘Team of the Tournament’ by Cricinfo for the 2007 T20I World Cup.

For his performances in 2007, he was named in the World T20I XI by Cricinfo.

Misbah played in 2008 Indian Premier League Season 1 for Royal Challengers Bangalore while he played in Sri Lanka Premier League for Kandurata Warriors in 2012. And he also represented St Lucia Zouks in 2013 season in Caribbean Premier League. He also played for Abhani in Bangladesh.

Earlier in 2010, after the Australia tour, he was dropped from all formats of the game and later was considering retiring if the selectors continue to ignore him. He was not considered for England tour where the spot-fixing saga happened due to which Salman Butt was banned, creating a captaincy hole in the team. Then in October 2010, surprisingly he was appointed the Pakistan’s Test captain for series against South Africa in UAE.

Misbah led the team in eight T20I matches. He won six and lost two. He played his last T20I match against England in 27 February 2012. After the defeat in Twenty20 series against England in 2012 and criticism from former cricketers, Misbah stepped down as Pakistan’s Twenty20 captain and Mohammad Hafeez was named his successor to lead the team in Twenty20.

In 2013, Misbah was brilliant in terms of his batting. He moved to a career-best seventh place in the ICC rankings for ODI batsmen. Misbah was the leading run scorer in ODI cricket with 1373 runs for year 2013 ahead of Mohammad Hafeez and Virat Kohli. He also had 15 ODI half centuries, which is a record for most ODI half centuries in a calendar year, as well as hitting 3rd most ODI sixes that year.

Despite, Pakistan losing all 3 of their games, h was named as part of the ‘Team of the Tournament’ in the 2013 Champions Trophy by the ICC. He was also named as captain of the Team by Cricinfo.

In 2013, Pakistan played bilateral series against South Africa, India, West Indies, Zimbabwe and Sri Lanka and they also participated in Champions Trophy. Despite winning against India in India, away series lose against South Africa 3–2, win-less streak in Champions Trophy and winning against minnow Zimbabwe 2–1 and then again defeat in home series against South Africa in UAE 4–1 put huge criticism on Misbah’s captaincy and his approach to the game. Especially series defeat against South Africa 4–1, brought Misbah’s captaincy under severe scrutiny. Ex-Pakistani players were demanding a total renovation of Pakistan cricket, and Misbah was being criticized for his captaincy, slow batting and the defeat. The PCB, however, announced that Misbah was to remain captain until the 2015 Cricket World Cup. Several TV shows and notable personalities opposed this decision and demanded that Misbah should be sacked.

In 2014, he made a test century off of 56 deliveries against Australia in Abu Dhabi, equaling the fastest one of that time by Viv Richards. In July 2016, Misbah scored a century against England at Lord’s and became the oldest cricketer in 82 years to score a test century. At the age of 42 years and 2 months, Misbah also became the oldest captain ever to score a test century. Misbah celebrated the landmark by saluting his team members and doing ten push-ups. He later explained during an interview that the celebration was meant as a tribute to the Military Boot Camp in Abbotabad where the team had attended an army style training session.

In 2015, Misbah signed by Rangpur Riders to play in the third edition of the Bangladesh Premier League. He made the decision to play in order to remain match fit for the upcoming Test Series with England in July 2016. In only his first game for Rangpur Riders, Misbah scored 61 runs, smashing 4 sixes and winning his team the game by chasing a mammoth total of 187. He was awarded the Man of the Match award for the performances.

Misbah was the ODI captain from 2008–2015 and had the 10th highest success rate. He left in 2015 as captain from criticism due to his slow yet successful approach. However, after continuous international losses, notably Pakistan’s exit from the 2016 ICC World Twenty20, PCB officials seriously considered asking him to return as ODI captain.

In January 2015, Misbah announced that he would retire from ODIs and T20Is after the 2015 World Cup. Misbah captained Pakistan in 2015 Cricket World Cup at Australia. He was the leading run scorer in tournament from Pakistan. Pakistan could only make it to Quarter-Finals. They were defeated by Australia in Quarter-Final, which was the last ODI match for Misbah.

Misbah signed by Islamabad United for a price of $140,000 to be played in February 2016 for Pakistan Super League. He is the 10th highest scorer in the league. He led Islamabad United to be the first champions of Pakistan Super League, and again was captain of the Islamabad United when the team won the third edition of PSL. Misbah also enjoys the highest success percentage as captain in Pakistan Super League matches up till now. In 2019 against the Lahore Qalandars, he became the oldest player in all of t20 cricket to score a 50.

In August 2016, under Misbah’s captaincy, Pakistan achieved the number 1 ranking in test cricket for the first time since 1988. Pakistan displaced India as number 1 after rain caused the final test match between India and West Indies to end in a draw. PCB chairman Shahryar Khan and ex-Pakistan coach Waqar Younis said that all credit should be given to Misbah for his leadership over the last six years.

In April 2016, Misbah decided to postpone his Test retirement until Australia tour in 2016/17. On 31 October Misbah ul-Haq ended his PSL career but soon took back his PSL retirement.

In November 2016, against New Zealand at Christchurch, Misbah-ul-Haq was handed over a one-match suspension by the ICC for his side’s slow over rate, meaning he had to miss the second Test in Hamilton. On 30 December 2016, Cricinfo published an article which indicated that Misbah might retire.

However, he continued to play in longer format for rest of the series with success, where Pakistan beat England to become No. 1 Test team in the world as well. On 6 April 2017, Misbah finally announced his intentions to retire from all international cricket after the conclusion of West Indies tour.

He played his last international match on May 10, 2017 against West Indies in Roseau. He scored his 39th Test fifty in the first innings, but dismissed for just 2 runs in the second innings. However, in his last match as captain, Pakistan won the match by 101 runs and sealed the series 2–1. The win highlighted as the first ever series win against West Indies in the West Indies as well.

On 4 September 2019, Misbah was appointed as the head coach for Pakistan cricket team as well as chief selector on a 3-year contract. This is the first time someone had simultaneously held both positions in Pakistan cricket. This started well for Misbah who won the One day international series 2–0. But then in the T20 series Sri Lanka pulled off a shock result and whitewashed Pakistan. Afterwards he led the team in Australia where they lost the test series 2-0.