Karachi last hosted a one-day international in 2009 during the fateful Sri Lanka tour to Pakistan that abruptly ended when militants attacked the visitors' team bus in Lahore.
The 10-year wait depriving Karachi the taste of ODI cricket will conclude when the depleted Sri Lanka squad takes on the hosts on Friday, bolstering the country's revival in international cricket.
Although 10 senior Sri Lankan players withdrew from the tour posing questions over the evenness of the contest, the mood is positive in the Pakistan camp with captain Sarfaraz Ahmed emphasizing on the emotional value of the historic event.
"History will be made on Friday when Karachi will host the first ODI. I can't wait for Friday," he said.
"We must thank the Sri Lankan team for touring us."
Amidst the rhetoric surrounding "stat-padding" for the Pakistan players, the tour presents a perfect opportunity for Sarfaraz's side to recoup their confidence following a disappointing World Cup campaign.
Pakistan narrowly missed out on qualifying for the semi-finals in the 50-over showpiece event but that was enough to trigger a spate of changes in the coaching personnel.
Former skipper Misbah-ul-Haq was handed the dual role of head coach and chief selector, replacing the outgoing Mickey Arthur.
With Misbah at the helm and a renewed focus on high fitness levels and discipline, it will be interesting to see how Pakistan recover from their dwindling form in ODI cricket since the Champions Trophy triumph two years ago.
The talk of the two-week tour has mostly been based on the security arrangements in place and the future of international cricket in Pakistan but Sri Lanka skipper Lahiru Thirimanne believes there are enough resources in the team to pull off, what most would refer to, an "upset".
"We still have a good team. I believe if we play to our potential we can do very well," he said on the eve of the match.
Sri Lanka completed a whitewash over Bangladesh in the home series in July but missing the likes of Angelo Mathews, Thisara Perera, Kusal Perera and Dimuth Karunaratne in the team, doubts persist over their ability to succeed.
The National Stadium, Karachi traditionally boasts flat surfaces offering little assistance to the bowlers hence the crux of the battle between both sides would be on their batting depth.
Pakistan's premier batsman Babar Azam is no stranger to international cricket at home - he made his ODI debut against Zimbabwe at Gaddafi Stadium in 2015.
Having established his reputation as Pakistan's batting mainstay, all eyes are on Babar as he requires 280 runs across the next three innings to displace Virat Kohli as the world No. 1 batsman.
Additionally, Babar's leadership skills will come to the fore for the first time in his short and ravishing career after he was named deputy to Sarfaraz for the six limited-overs fixtures.
Sri Lanka's find of the World Cup, Avishka Fernando led a masterful display of elegant strokes throughout the tournament including a fine century against the West Indies.
The 21-year-old, still finding his feet in the international arena, looks a promising talent who could nullify Pakistan's all-round bowling attack.
Sri Lanka's meek middle order has been an issue plaguing their ODI team but Fernando's potential heroics at the top can protect them from imminent implosion.
Pakistan: Sarfaraz Ahmed (c), Babar Azam (vc), Abid Ali, Asif Ali, Fakhar Zaman, Haris Sohail, Mohammad Hasnain, Iftikhar Ahmed, Imad Wasim, Mohammad Amir, Mohammad Nawaz, Mohammad Rizwan, Shadab Khan, Usman Shinwari, Wahab Riaz
Sri Lanka: Lahiru Thirimanne (c), Danushka Gunathilaka, Sadeera Samarawickrama, Avishka Fernando, Oshada Fernando, Shehan Jayasuriya, Dasun Shanaka, Minod Bhanuka, Angelo Perera, Wanindu Hasaranga, Lakshan Sandakan, Nuwan Pradeep, Isuru Udana, Kasun Rajitha, Lahiru Kumara